Insilico Medicine

Scientific assessment

Contents

TNIK in Neuropathic Pain — Target Evaluation

Dated 2026-08-20

Assessment

Executive Summary

The recommendation for this target in neuropathic pain is: monitor.

TNIK is a well-validated, structurally tractable kinase with a clinical-stage inhibitor, and in neuropathic pain it offers a genuinely novel, potentially disease-modifying mechanism: dampening spinal AMPA-receptor potentiation and central sensitization rather than blocking peripheral excitability. What it lacks is depth of disease evidence, because the pain rationale is a single preclinical cascade, no transcriptomic data exist for the indication, and the high central-nervous-system expression of the target makes cognition the dominant on-target risk.

MonitorrecommendationThe full grounds are set out in the verdict section, with what would change the answer.
Highon-target safety riskThe worst of the graded dimensions in the safety section; the rows behind it are below.
3programs against this targetCounted across all diseases in the competitive section, where each is listed.
6patent filingsThe filings a program here would have to work around, listed in the competitive section.

The evidence

Current state of the evidence

TNIK-neuropathic pain evaluationCautionScientifically attractive and first-in-class in pain, but the target-in-disease link rests on one preclinical mechanistic thread with no omics or clinical support.

“The disease rationale rests almost entirely on one preclinical mechanistic body of work (PMID: 26674878); paralog active-site identity percentages were not quantified by the tools used; GWAS trait labels were not returned; and the human safety readout that de-risks the target comes from a different indication (IPF), not pain.”

HTML

The reasoning

The evaluation recommends monitoring TNIK in neuropathic pain: druggability is high and the competitive and patent space is open, but expression evidence is absent, the on-target cognitive liability is high, and the pain rationale rests on a single preclinical body of work, so pursuit waits on independent anti-allodynia validation and an exposure strategy that spares the brain.

Table 1Each line of evidence is set out with the ground it covers and the position it supports.
EvidenceScopePosition
TNIK-neuropathic pain evaluationA single-target evaluation of TNIK scoped to neuropathic pain (the PandaOmics-resolved entity neuralgia), covering target biology, disease-specific evidence, mechanism of action, druggability, on-target safety, and the competitive and patent landscape.argues for, with conditions

Positions record where each line of evidence lands on the question this page asks rather than on the target in general.

Safety

The cost of inhibiting the target

Highon-target riskAcross five dimensions the grades run one high, two moderate and two low, and the summary takes the worst of them because a patient meets all of them at once.
1tissues at high riskOf the four tissues in which the gene’s level has been reported, a tissue counts as at risk where the gene is present and its job there is one that nothing else does.
2close relativesA close relative is a protein similar enough to the target that a molecule designed against the target may bind it as well.
Table 2Each safety dimension is set out with the evidence it rests on and the measures that would reduce it.
DimensionRiskUnderlying evidenceMitigation
KO lethalityLowGermline KO mice viable, not embryonic lethalSystemic inhibition tolerable in principle
Essential tissue functionHighHigh CNS expression with non-redundant synaptic/cognitive roles; human LoF causes cognitive disabilityPeripheral restriction or spinal/local delivery; shallow/reversible inhibition
Paralog cross-reactivityModerateClose paralogs MINK1/MAP4K4 share the ATP pocketStructure-guided selectivity; counter-screen the paralog panel
Immune system effectsModerateTNIK imprints CD8+ T-cell memory (PMID: 32242021)Monitor immune endpoints on chronic dosing
Reproductive toxicityLowNo reproductive KO phenotype retrievedStandard reproductive-tox package

The five graded dimensions stand at one high, two moderate and two low.

Table 3Each tissue in which the gene is expressed is listed with the cost that blocking it there would carry.
TissueReported levelas a tissue expression atlas reports itFunction in that tissueRisk if inhibitedjudged here, not measured
Brain / CNS neuronsHighDendrite/synapse development; AMPA-receptor regulation; cognitionHigh
Intestine / proliferative epitheliaMediumWnt/TCF4-dependent crypt renewalModerate
Platelets / hematopoieticMediumIntegrin αIIbβ3 signaling (PMID: 41246457)Moderate
Immune (T cells)MediumCD8+ T-cell memory imprinting (PMID: 32242021)Moderate

The two right-hand columns are deliberately on different scales, because one records a level that was measured while the other states the conclusion drawn from that level here.

Table 4Each relative listed here is close enough to the target that a molecule aimed at the target might bind it as well.
RelativeIdentitypercent, over the region named beside itRegion comparedOverlapping functionSelectivity risk
MINK1not quantifiednot comparedClosest GCK-IV kinase; shares ATP-pocket architecture; overlapping neuronal rolesHigh
MAP4K4not quantifiednot comparedGCK-IV kinase; frequent co-inhibition by ATP-competitive TNIK chemotypesModerate

Identity is quoted over a named region rather than the whole protein: two proteins can share little overall and almost everything where a drug would bind.

Consequences of losing the gene, in two models
  • Mouse, Germline KO: Viable. Behavioral/cognitive alterations; not grossly lethal.
  • Human, Biallelic LoF variants: Viable. Autosomal-recessive cognitive disability.

Competition

Other programs against this target

0programs in this diseaseNo compound against this target is in development for neuropathic pain, so the table below is empty because the field is empty rather than because the search was narrow.
3programs elsewherePrograms aimed at the same target in other diseases show that the target can be drugged, although they are not evidence that drugging it helps here.
6patent filingsSix filings were made against this target, running from 2009 to 2021.
Nothing is in development for neuropathic pain

No compound against this target is in development for neuropathic pain, so the table below is empty because the field is empty rather than because the search was narrow.

Table 5The programs listed here act on the same target but are aimed at other diseases.
Compounds and biologicsTypeAction on the targetStageStatusDeveloperEvidenceDisease
RentosertibSmall moleculeinhibitPhase 3Not yet recruitingInsilico MedicineOral AI-designed TNIK inhibitorIdiopathic pulmonary fibrosis
NCB-0846Small moleculeinhibitPreclinicalOngoingCarna Biosciences / NCC JapanATP-competitive TNIK inhibitorOncology
KY-05009Small moleculeinhibitPreclinicalPreclinicalAcademicaminothiazole TNIK inhibitorOncology / EMT

They are listed so that it is clear who holds what, although none of it is evidence about this disease.

Table 6These are the filings that a program in this disease would have to work around.
FilingFiledHolderScope of the claimsApproach
WO2022034587A12021TNIK Therapeutics LtdComposition-of-matter and method-of-treatmentA novel TNIK inhibitor chemotype with cancer as the primary claimed use.
US11530197B22021Insilico Medicine (the CEO named as inventor)Composition-of-matter and method-of-treatmentTNIK and/or MAP4K4 inhibitors for epithelial-mesenchymal transition, fibrosis, and cancer through transforming growth factor beta signaling.
US10294207B22015Green Cross Corp / Soongyu ChoiComposition-of-matter and method-of-treatmentA multi-kinase inhibitor for cancers including brain cancer and for chronic inflammation.
WO2019156439A12018UndisclosedMethod-of-treatmentCancer plus chronic obstructive pulmonary disease, lupus nephritis, diabetic nephropathy, focal segmental glomerulosclerosis, and pulmonary and renal fibrosis.
WO2013176293A12013Carna Biosciences / National Cancer Center JapanComposition-of-matterBicyclic thiazole TNIK inhibitors for solid cancers, the chemotype behind NCB-0846.
WO2010064111A12009Undisclosed (foundational)Method-of-treatmentFoundational TNIK and Wnt-TCF4 anti-cancer intellectual property.

Six filings were made against this target, running from 2009 to 2021.

Caveats

Challenges and Limitations

No omics or human evidence in this indication

PandaOmics holds no transcriptomic dataset for the neuralgia entity that neuropathic pain resolves to, so the multi-omics scoring engine could not be applied and the expression and omics layers are empty by data availability rather than by a negative result.

A single mechanistic source

The disease rationale rests almost entirely on one preclinical body of work (PMID: 26674878), with no independent replication and no human corroboration in pain.

Safety readout comes from a different indication

The human safety data that de-risk the target come from the idiopathic pulmonary fibrosis program for rentosertib, not from pain, and all efficacy claims in pain are preclinical and rodent-derived.

Paralog identity not quantified

Pairwise active-site identity to the closest paralogs MINK1 and MAP4K4 was not quantified by the tools used, so selectivity risk is assessed qualitatively from shared ATP-pocket architecture.

Verdict

Recommendation and next steps

MonitorrecommendationScientifically attractive and first-in-class in pain, but too early to pursue until independent preclinical anti-allodynia validation and an exposure strategy that spares the brain are in hand.
3routes consideredEach route is scored for feasibility, novelty and selectivity against this target in neuropathic pain.
Rank of this disease among the target’s indications

Three of the four indications ranked for this target score above neuropathic pain, namely neoplasm and cancer, nervous system disease and schizophrenia.

Table 7The recommendation rests on the judgments set out here.
AssessmentRatingGrounds for the rating
Overall druggabilityHighA well-validated kinase with many solved structures, inhibitor co-crystals, and a clinical-stage inhibitor already in trials.
On-target safetyHighThe target is knockout-viable with human safety data in idiopathic pulmonary fibrosis, but high central-nervous-system expression and a human loss-of-function cognitive phenotype make cognition a dominant on-target liability.
Expression evidenceNo dataPandaOmics has no transcriptomic dataset for the neuralgia entity, so expression evidence is absent rather than weak.
OpportunityModerateA genuinely novel, potentially disease-modifying mechanism in a high-unmet-need indication.
RiskHighTarget-in-disease validation rests on a single preclinical thread with no omics or clinical support.
Competitive intensityLowNo TNIK program exists in pain, leaving first-in-class white space.
Intellectual-property white spaceHighNo located patent claims a neuropathic-pain or analgesic use, pending a formal freedom-to-operate analysis.

The expression rating is derived from the datasets themselves, so it is identical to the one reported in the evidence section above.

Table 8Each route is scored out of ten on three separate counts.
RouteFeasibleNovelSelectiveRequirements
Small molecule, peripherally or spinally restricted795Lead option; pursue only after preclinical anti-allodynia proof.
Small molecule, central-nervous-system-penetrant695Higher efficacy potential but cognition risk; deprioritize versus the restricted approach.
Antisense or short interfering RNA, intrathecal488Selectivity advantage; delivery and durability unproven.

Ten is the top of each scale, and a route scoring well on all three is not thereby the one to take, because the scores say what is possible rather than what this program is set up to do.

The work each route would require

Each route scored above is set out with the result that would settle whether it works.

  1. Small molecule, peripherally or spinally restricted

    A first-in-class, non-opioid, non-ion-channel analgesic acting on the spinal TRAF2-TNIK-GluR1 AMPA-receptor axis, restricting exposure to the periphery and spinal compartment to spare brain TNIK. This quarter, run rentosertib or NCB-0846 in a standard spinal-nerve-ligation allodynia model with a GluA1-phosphorylation readout.

    What would rule it out: No-go if efficacy requires brain exposure at cognition-impairing levels.Target-validation and pharmacokinetic-restriction work in 1 to 2 years, investigational-new-drug-enabling in 3 to 4 years, and Phase 2 proof-of-concept in 5 to 6 years.
  2. Small molecule, central-nervous-system-penetrant

    A brain-penetrant inhibitor could maximize central anti-sensitization efficacy using rentosertib-class chemistry directly, should dorsal-horn engagement prove insufficient with a restricted molecule. This quarter, build a cognition versus anti-allodynia dose-response in parallel.

    What would rule it out: Stop the approach if anti-allodynia and cognitive endpoints overlap with no therapeutic index between them.Investigational-new-drug-enabling in 3 to 4 years contingent on a cognition-safety margin, and Phase 2 proof-of-concept in 5 to 7 years.
  3. Antisense or short interfering RNA, intrathecal

    Local intrathecal knockdown could achieve dorsal-horn-restricted TNIK suppression with oligonucleotide-grade selectivity, side-stepping the paralog ATP-pocket problem. This quarter, design and screen spinally delivered TNIK antisense oligonucleotides or short interfering RNA in a nerve-injury model.

    What would rule it out: Abandon the route on unacceptable local neurotoxicity.Tool-oligonucleotide proof-of-concept in 1 to 2 years and investigational-new-drug-enabling in 4 to 5 years.
Table 9The obstacles this program would meet are listed with the measures that would reduce them.
ChallengeSeverityMitigation
No omics or human evidence for TNIK in neuropathic painHighGenerate in-house transcriptomic and functional data in nerve-injury models before committing.
A single mechanistic literature source underpins the hypothesisHighSeek independent replication in two or more models and species before program initiation.
On-target central-nervous-system and cognition liabilityHighUse peripheral or spinal restriction, shallow and reversible inhibition, and defined cognition safety margins.
Paralog selectivity against MINK1 and MAP4K4ModerateApply structure-guided design against the solved co-crystals and paralog counter-screens.
A crowded, ion-channel-focused pain fieldModeratePosition the program as disease-modifying and orthogonal, and target refractory neuropathic pain.

Five challenges are raised in all, graded three high and two moderate.

Literature cited

References

Primary literature

  1. Lin TB, Hsieh MC, Lai CY et al. (2015) Fbxo3-Dependent Fbxl2 Ubiquitination Mediates Neuropathic Allodynia through the TRAF2/TNIK/GluR1 Cascade. J NeurosciPMID 26674878 doi:10.1523/JNEUROSCI.2301-15.2015
  2. Ravisangar V, Bowie J, Salih M et al. (2026) A Systematic Review Exploring the link between Chronic Venous Disease and Neuropathy. J Vasc Surg Venous Lymphat DisordPMID 42617732 doi:10.1016/j.jvsv.2026.102602
  3. Li X, Liu H (2026) Trigger zones in trigeminal neuralgia: clinical features, pathophysiological mechanisms, and therapeutic strategies. Front NeurolPMID 42601888 doi:10.3389/fneur.2026.1838454
  4. Galimberti G, Riboldi B, Amodeo G et al. (2026) Pain in Fabry disease: do experimental models reveal novel therapeutic targets? Biochem PharmacolPMID 42562339 doi:10.1016/j.bcp.2026.118323
  5. Freynhagen R, Morlion B, Alcántara Montero A et al. (2026) Mixed Pain: Toward a Consensus Definition and a Mechanism-Based Framework. Eur J PainPMID 42559696 doi:10.1002/ejp.70356
  6. Haag N, Körner J (2026) Sensory neuron heterogeneity in neuropathic pain: implications for precision analgesia. Curr Opin Support Palliat CarePMID 42544932 doi:10.1097/SPC.0000000000000808
  7. García-Domínguez M (2026) Neuroligins and Neuropathic Pain: Insights into Synaptic Plasticity and Pain Transmission. Biology (Basel)PMID 42510726 doi:10.3390/biology15141180
  8. Cascella M, De Simone M, Vittori A et al. (2026) An overview of current and emerging strategies for phantom limb pain. Expert Rev NeurotherPMID 42507616 doi:10.1080/14737175.2026.2709803
  9. Nasir A, Khan T, Anam et al. (2026) Insights into neuropathic pain: From disease models to therapeutic interventions. Neurosci Biobehav RevPMID 42498091 doi:10.1016/j.neubiorev.2026.106878
  10. Lai CY, Hsieh MC, Chou D et al. (2024) The Transcription Factor Tbx5-Dependent Epigenetic Modification Contributes to Neuropathic Allodynia by Activating TRPV1 Expression in the Dorsal Horn. J NeurosciPMID 39174351 doi:10.1523/JNEUROSCI.0497-24.2024
  11. Lai CY, Ho YC, Hsieh MC et al. (2016) Spinal Fbxo3-Dependent Fbxl2 Ubiquitination of Active Zone Protein RIM1α Mediates Neuropathic Allodynia through CaV2.2 Activation. J NeurosciPMID 27629721 doi:10.1523/JNEUROSCI.1732-16.2016
  12. Hussain NK, Hsin H, Huganir RL et al. (2010) MINK and TNIK differentially act on Rap2-mediated signal transduction to regulate neuronal structure and AMPA receptor function. J NeurosciPMID 21048137 doi:10.1523/JNEUROSCI.4124-10.2010
  13. Namboothiri DR, Sivanandan A, Netto G et al. (2026) Artificial intelligence in the development of Rentosertib: A novel TNIK inhibitor for idiopathic pulmonary fibrosis - A letter to editor. Pulm Pharmacol TherPMID 41475169 doi:10.1016/j.pupt.2025.102405
  14. Xu Z, Ren F, Wang P et al. (2025) A generative AI-discovered TNIK inhibitor for idiopathic pulmonary fibrosis: a randomized phase 2a trial. Nat MedPMID 40461817 doi:10.1038/s41591-025-03743-2
  15. Jaeger-Ruckstuhl CA, Hinterbrandner M, Höpner S et al. (2020) TNIK signaling imprints CD8(+) T cell memory formation early after priming. Nat CommunPMID 32242021 doi:10.1038/s41467-020-15413-7
  16. Niu X, Zhang S, Xu B et al. (2026) Discovery of potent TNIK inhibitors containing a 1H-pyrrolo[2,3-b]pyridine scaffold as promising therapeutics for colorectal cancer. Eur J Med ChemPMID 41818865 doi:10.1016/j.ejmech.2026.118717
  17. Kukimoto-Niino M, Shirouzu M, Yamada T (2022) Structural Insight into TNIK Inhibition. Int J Mol SciPMID 36361804 doi:10.3390/ijms232113010
  18. Zhou K, Cheong JE, Krishnaji ST et al. (2023) Inhibition of Wnt Signaling in Colon Cancer Cells via an Oral Drug that Facilitates TNIK Degradation. Mol Cancer TherPMID 36302395 doi:10.1158/1535-7163.MCT-21-0801
  19. Yan R, Zhu H, Huang P et al. (2022) Liquidambaric acid inhibits Wnt/β-catenin signaling and colon cancer via targeting TNF receptor-associated factor 2. Cell RepPMID 35108540 doi:10.1016/j.celrep.2022.110319
  20. Yamada T, Masuda M (2017) Emergence of TNIK inhibitors in cancer therapeutics. Cancer SciPMID 28208209 doi:10.1111/cas.13203
  21. Ho KK, Parnell KM, Yuan Y et al. (2013) Discovery of 4-phenyl-2-phenylaminopyridine based TNIK inhibitors. Bioorg Med Chem LettPMID 23232060 doi:10.1016/j.bmcl.2012.11.013
  22. Tanimoto A, Ramkumar K, Stewart CA et al. (2026) The Impact of Targeting TRAF2 and NCK-Interacting Protein Kinase on Antitumor Effect and Tumor Immune Environment in c-MYC-High SCLC. J Thorac OncolPMID 41456708 doi:10.1016/j.jtho.2025.12.102
  23. Puleo N, Ram H, Dziubinski ML et al. (2025) Identification of a TNIK-CDK9 Axis as a Targetable Strategy for Platinum-Resistant Ovarian Cancer. Mol Cancer TherPMID 39873147 doi:10.1158/1535-7163.MCT-24-0785
  24. Zhang R, Yu Y, Yang Y et al. (2024) Therapeutic targeting of TNIK in papillary thyroid carcinoma: a novel approach for tumor growth suppression. Med OncolPMID 38763968 doi:10.1007/s12032-024-02380-y
  25. Jung HR, Oh Y, Na D et al. (2021) CRISPR screens identify a novel combination treatment targeting BCL-X(L) and WNT signaling for KRAS/BRAF-mutated colorectal cancers. OncogenePMID 33846570 doi:10.1038/s41388-021-01777-7
  26. Sugano T, Masuda M, Takeshita F et al. (2021) Pharmacological blockage of transforming growth factor-β signalling by a Traf2- and Nck-interacting kinase inhibitor, NCB-0846. Br J CancerPMID 33244122 doi:10.1038/s41416-020-01162-3
  27. Sekita T, Yamada T, Kobayashi E et al. (2020) Feasibility of Targeting Traf2-and-Nck-Interacting Kinase in Synovial Sarcoma. Cancers (Basel)PMID 32429395 doi:10.3390/cancers12051258
  28. Jiang J, Wilkinson B, Flores I et al. (2024) Mutations in the postsynaptic density signaling hub TNIK disrupt PSD signaling in human models of neurodevelopmental disorders. Front Mol NeurosciPMID 38638602 doi:10.3389/fnmol.2024.1359154
  29. Gal J, Chen J, Katsumata Y et al. (2018) Detergent Insoluble Proteins and Inclusion Body-Like Structures Immunoreactive for PRKDC/DNA-PK/DNA-PKcs, FTL, NNT, and AIFM1 in the Amygdala of Cognitively Impaired Elderly Persons. J Neuropathol Exp NeurolPMID 29186589 doi:10.1093/jnen/nlx097
  30. Coba MP, Komiyama NH, Nithianantharajah J et al. (2012) TNiK is required for postsynaptic and nuclear signaling pathways and cognitive function. J NeurosciPMID 23035106 doi:10.1523/JNEUROSCI.2433-12.2012
  31. MacLaren EJ, Charlesworth P, Coba MP et al. (2011) Knockdown of mental disorder susceptibility genes disrupts neuronal network physiology in vitro. Mol Cell NeurosciPMID 21440632 doi:10.1016/j.mcn.2010.12.014
  32. Yoo W (2026) Precision oncology in the age of AI: lessons from AI-driven drug discovery and clinical translation. BJC RepPMID 41986665 doi:10.1038/s44276-026-00221-1
  33. Zhao L, Liu H, Yao X et al. (2025) Integrated Machine Learning and Structure-Based Virtual Screening Identify Osimertinib as a TNIK Inhibitor for Idiopathic Pulmonary Fibrosis. J Chem Inf ModelPMID 40999821 doi:10.1021/acs.jcim.5c01521
  34. Qin L, Aladinskiy V, Gennert D et al. (2025) Traf2- and Nck-interacting kinase inhibitors: a patent review (2008-2024). Expert Opin Ther PatPMID 40820280 doi:10.1080/13543776.2025.2548585
  35. Bull LJ, Spencer S, Bedi R et al. (2025) TRAF2 and NCK interacting kinase: a novel regulator of integrin α(IIb)β(3) signaling in platelets. Res Pract Thromb HaemostPMID 41246457 doi:10.1016/j.rpth.2025.103204
  36. Lee Y, Jung JI, Park KY et al. (2017) Synergistic inhibition effect of TNIK inhibitor KY-05009 and receptor tyrosine kinase inhibitor dovitinib on IL-6-induced proliferation and Wnt signaling pathway in human multiple myeloma cells. OncotargetPMID 28467797 doi:10.18632/oncotarget.17056
  37. Kim J, Moon SH, Kim BT et al. (2014) A novel aminothiazole KY-05009 with potential to inhibit Traf2- and Nck-interacting kinase (TNIK) attenuates TGF-β1-mediated epithelial-to-mesenchymal transition in human lung adenocarcinoma A549 cells. PLoS OnePMID 25337707 doi:10.1371/journal.pone.0110180
  38. Bravo AL, Ajala SI, Ayo MF et al. (2026) From ion channel biology to clinical practice: suzetrigine as a precision analgesic. Front Med (Lausanne)PMID 42591799 doi:10.3389/fmed.2026.1897421
  39. Habib AS, Solanki D, Hoff J et al. (2026) Suzetrigine as Part of Multimodal Therapy Enables Opioid-Free Recovery after Laparoscopic or Arthroscopic Procedures. Pain TherPMID 42570176 doi:10.1007/s40122-026-00865-4
  40. Dextras C, Compton P (2026) Suzetrigine: A New and Novel Analgesic for Acute Pain. Pain Manag NursPMID 42476867 doi:10.1016/j.pmn.2026.06.017
  41. Lin SJ, McCoun J, Solanki D et al. (2026) Suzetrigine as Part of Multimodal Therapy Enables Opioid-Free Recovery After Aesthetic or Reconstructive Procedures. Plast Reconstr SurgPMID 42468001 doi:10.1097/PRS.0000000000013299
  42. Cui A, Meng X, Wang Z et al. (2026) Dorsal Root Ganglion as a Hub for Peripheral Sensitization: A Hierarchical Regulation Model and Translational Progress. J Pain ResPMID 42454000 doi:10.2147/JPR.S601365
  43. Anazi S, Shamseldin HE, AlNaqeb D et al. (2016) A null mutation in TNIK defines a novel locus for intellectual disability. Hum GenetPMID 27106596 doi:10.1007/s00439-016-1671-9
  44. Kot A, Koszewska D, Ochman B et al. (2024) Clinical Potential of Misshapen/NIKs-Related Kinase (MINK) 1-A Many-Sided Element of Cell Physiology and Pathology. Curr Issues Mol BiolPMID 39727954 doi:10.3390/cimb46120826
  45. Gui J, Li Z, Zhou X (2013) Dynamic change of TNIK in response to tumor necrosis factor alpha in a TRAF2-dependent manner. Hum CellPMID 23355318 doi:10.1007/s13577-012-0058-z
  46. Gui J, Yang B, Wu J et al. (2011) Enormous influence of TNIK knockdown on intracellular signals and cell survival. Hum CellPMID 21710359 doi:10.1007/s13577-011-0023-2
  47. Burette AC, Phend KD, Burette S et al. (2015) Organization of TNIK in dendritic spines. J Comp NeurolPMID 25753355 doi:10.1002/cne.23770
  48. Jain A, Sadik E, Cardenas-Rojas A et al. (2026) Chronic Pain in Elderly Patients: Pathophysiology, Pharmacologic and Non-Pharmacologic Therapies, and Interventional Management. Clin PharmacolPMID 41978902 doi:10.2147/CPAA.S506172
  49. Yuan R, Li Y, Li X et al. (2024) Transcriptome analysis to explore the mechanism of downregulated TNIK influencing the effect of risperidone. Front PharmacolPMID 39268461 doi:10.3389/fphar.2024.1431923
  50. Xu Q, Li Y, Li M et al. (2022) The influence of TNIK gene polymorphisms on risperidone response in a Chinese Han population. PharmacogenomicsPMID 35698907 doi:10.2217/pgs-2022-0052
  51. Nie FY, Zhang MR, Shang SS et al. (2021) Methylome-wide association study of first-episode schizophrenia reveals a hypermethylated CpG site in the promoter region of the TNIK susceptibility gene. Prog Neuropsychopharmacol Biol PsychiatryPMID 32853717
  52. Gumina V, Colombrita C, Fallini C et al. (2019) TDP-43 and NOVA-1 RNA-binding proteins as competitive splicing regulators of the schizophrenia-associated TNIK gene. Biochim Biophys Acta Gene Regul MechPMID 31382054
  53. Read J, Collie IT, Nguyen-McCarty M et al. (2019) Tool inhibitors and assays to interrogate the biology of the TRAF2 and NCK interacting kinase. Bioorg Med Chem LettPMID 31153805 doi:10.1016/j.bmcl.2019.05.032
  54. Allen JD, Bishop JR (2019) A systematic review of genome-wide association studies of antipsychotic response. PharmacogenomicsPMID 30883267 doi:10.2217/pgs-2018-0163
  55. Yu H, Yan H, Wang L et al. (2018) Five novel loci associated with antipsychotic treatment response in patients with schizophrenia: a genome-wide association study. Lancet PsychiatryPMID 29503163 doi:10.1016/S2215-0366(18)30049-X
  56. Xu Q, Wu X, Li M et al. (2016) Association studies of genomic variants with treatment response to risperidone, clozapine, quetiapine and chlorpromazine in the Chinese Han population. Pharmacogenomics JPMID 26282453 doi:10.1038/tpj.2015.61
  57. Kawabe H, Neeb A, Dimova K et al. (2010) Regulation of Rap2A by the ubiquitin ligase Nedd4-1 controls neurite development. NeuronPMID 20159449 doi:10.1016/j.neuron.2010.01.007