THERAPY DOSSIER · th-bc7b07a463bf

NA101, a selective calpain-2 inhibitor; nilotinib, a brain-penetrant c-Abl inhibitor, tested separately

Drug · Tyrosine-protein kinase ABL inhibitor; Bcr/Abl fusion protein inhibitor (INHIBITOR, direct interaction)

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Evidence & regulatory context

Mechanism: Tyrosine-protein kinase ABL inhibitor; Bcr/Abl fusion protein inhibitor (INHIBITOR, direct interaction)
Target: CHEMBL1862 (ABL tyrosine kinase); CHEMBL2096618 (Bcr/Abl fusion protein)
Injury models: TBI · Chemical/toxin
Reported indication: Not recorded
First approval: 2007
Development stage: Not recorded
ChEMBL record: CHEMBL255863 ↗
ChEMBL max phase: 4 / 4 (development scale, not regulatory approval)
Synonyms: AMN 107; AMN-107; AMN107; Nilotinib; NSC-747599; Tasigna
Note: Not recorded

Clinical trials 16

1 linked trials carry an injury-indication flag. These flags support record-level exploration and sit alongside the stringent aggregate counts described in Methods.

NCT01914484 ↗Injury indicationPHASE1/PHASE2completed

Phase I/II Ruxolitinib + Nilotinib in Ph+ CML/ALL Failing TKI Therapy

Chronic Myeloid Leukemia · Philadelphia Positive Acute Lymphoblastic Leukemia

Enrolment: 4 · Results not recorded

NCT03784014 ↗PHASE3completed

Molecular Profiling of Advanced Soft-tissue Sarcomas. A Phase III Study

Soft Tissue Sarcoma

Enrolment: 603 · Results not recorded

NCT02272777 ↗PHASE3completed

Open-label Imatinib and Nilotinib in Ph+ CP-CML (extension)

Leukemia

Enrolment: 225 · Results not recorded

NCT03516279 ↗PHASE2active not recruiting

Phase II Study of Adding Anti-PD-1 Pembrolizumab to Tyrosine Kinase Inhibitors in CML with Persistent MRD

Chronic Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive · Minimal Residual Disease

Enrolment: 40 · Results not recorded

NCT05564377 ↗PHASE2recruiting

Molecular Analysis for Combination Therapy Choice (ComboMATCH)

Advanced Malignant Solid Neoplasm · Metastatic Malignant Solid Neoplasm

Enrolment: 2900 · Results not recorded

NCT01806571 ↗PHASE2completed

Phase II Daunorubicin, Cytarabine and Nilotinib (Tasigna) in Newly Diagnosed AML with KIT Overexpression

Untreated Adult Acute Myeloid Leukemia

Enrolment: 34 · Results not recorded

NCT02353728 ↗PHASE2completed

Detection, Monitoring and Molecular Characterization of Leukemic Stem Cells in CML Undergoing Nilotinib Therapy

Chronic Myeloid Leukemia

Enrolment: 16 · Results not recorded

NCT01844765 ↗PHASE2completed

Phase II Oral Nilotinib in Pediatric Ph+ CML

Philadelphia Positive (Ph+) Chronic Myelogenous Leukemia

Enrolment: 59 · Results not recorded

NCT04626024 ↗PHASE2active not recruiting

TKI Cessation (incl. Nilotinib) for CML With Stable Molecular Response

Chronic Myeloid Leukemia

Enrolment: 17 · Results not recorded

NCT00129740 ↗PHASE2completed

Therapy of Early Chronic Phase CML With Oral Nilotinib

Leukemia, Myelogenous, Chronic

Enrolment: 148 · Results not recorded

NCT01261429 ↗PHASE2completed

Phase II Nilotinib in Pigmented Villonodular Synovitis/TGCT

Pigmented Villonodular Synovitis

Enrolment: 50 · Results not recorded

NCT01856283 ↗PHASE2completed

Phase II Nilotinib 300mg BID in Newly Diagnosed CP-CML

Leukemia, Myeloid, Chronic-Phase

Enrolment: 87 · Results not recorded

NCT01866553 ↗PHASE2terminated

Phase II Nilotinib + Pegylated Interferon-a2b in CML (NordDutchCML009)

Chronic Myeloid Leukemia

Enrolment: 20 · Results not recorded

NCT04903119 ↗PHASE1recruiting

Phase 1 Study of Nilotinib with Dabrafenib/Trametinib or Encorafenib/Binimetinib in BRAF V600 Mutant Metastatic Melanoma

Metastatic Melanoma · BRAF Gene Mutation

Enrolment: 30 · Results not recorded

NCT01871311 ↗PHASE1terminated

Phase I Study of Nilotinib and Cetuximab in Solid Tumors Treatable with Cetuximab

Colorectal Cancer · Head and Neck Cancer

Enrolment: 15 · Results not recorded

NCT01702064 ↗PHASE1completed

Phase I Ruxolitinib + Nilotinib in CML With Molecular Disease

Chronic Phase Chronic Myeloid Leukemia

Enrolment: 11 · Results not recorded

Preclinical evidence 2

2 studies reported at therapy level; 2 evidence entries itemised.

PMID 28924170 ↗2017Reported benefit

The tyrosine phosphatase PTPN13/FAP-1 links calpain-2, TBI and tau tyrosine phosphorylation.

MouseTBIControlled cortical impactC57Bl/6 wild type and calpain-1 knockout on C57Bl/6 backgroundIntraperitoneal injectionNA101 0.3 mg/kg; nilotinib dose not stated1 h after traumatic brain injury

Model: Controlled cortical impact after 5 mm craniotomy, 3 mm impactor tip, impact velocity 3 m/s, cortical deformation depth 0.5 mm

NA101 given 1 h after controlled cortical impact largely prevented PTPN13 and spectrin truncation and the rise in c-Abl Tyr245 and tau tyrosine phosphorylation at 6 h, and both NA101 and nilotinib significantly reduced tau oligomer accumulation in ipsilateral cortex and hippocampus at 24 h. NA101 a…

Extraction: extract · Subtype source: rule · Supplied extraction confidence: 0.85. Machine-extracted fields require source verification.

PMID 27975299 ↗2016Reported benefit

Nilotinib, a tyrosine kinase inhibitor exhibits protection against acute pancreatitis-induced lung and liver damage in rats.

RatChemical/toxinSprague-DawleyMale

Model: Acute pancreatitis induced with L-arginine, with secondary lung and liver injury

Acute pancreatitis produced marked deterioration in serum enzymes, nitric oxide, total protein and transforming growth factor beta1, raised tissue lipid peroxidation, reduced superoxide dismutase and glutathione, and caused oedema, haemorrhage, perivascular inflammation and acinar cell necrosis wit…

Extraction: extract · Supplied extraction confidence: 0.65. Machine-extracted fields require source verification.

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