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Table 1 Summary of the basic profile of type I AXL inhibitors and the related ongoing clinical trials

From: AXL receptor tyrosine kinase as a promising anti-cancer approach: functions, molecular mechanisms and clinical applications

Drug Developer Target(s)a IC50 for AXL Clinical Trial No.b Phase of approval Indications Monotherapy/Combinations Adverse events Status
BGB324 (R428) Rigel Pharmaceuticals/BerGen BIO AXL (selective) IC50 (in vitro) = 14 nM IC50 (in cells) = 14 nM NCT02424617 I/II NSCLC + Erlotinib Not reported Recruiting
NCT03184558 II TNBC + Pembrolizumab   Recruiting
NCT02488408 Ib/II AML, MDS ± Cytarabine/decitabine   Recruiting
NCT02872259 Ib/II Metastatic melanoma + Pembrolizumab; + Dabrafenib and trametinib   Recruiting
NCT03649321 Ib/II Pancreatic cancer ± Nab-paclitaxel/gemcitabine/cisplatin   Recruiting
NCT03824080 II MDS Monotherapy   Recruiting
TP-0903 Tolero Pharmaceuticals AXL (selective) IC50 (in vitro) = 27 nM IC50 (in cells) = 222 nM NCT03572634 I/II CLL ± Ibrutinib Not reported Not yet recruiting
NCT02729298 I Advanced solid tumors Monotherapy   Recruiting
Crizotinib (PF-02341066, marketed as [Xalkori]) Pfizer MET, ALK, RON, AXL IC50 (in vitro) = 294 nM IC50 (in vivo) = 322 nM NCT02737501 III ALK-positive locally advanced or metastatic NSCLC Crizotinib vs. Brigatinib Abdominal pain, headache, pyrexia, pain in extremity, nausea Active, not recruiting
NCT02223819 II Uveal melanoma Monotherapy Active, not recruiting
NCT02435108 II MET-positive gastric cancer Monotherapy Completed
NCT02207504 I Castration-resistant prostate cancer + Enzalutamide Active, not recruiting
Bosutinib (SKI-606, Bosulif®) Pfizer ABL, SRC, AXL IC50 (in vitro) = 174 nM NCT02228382 IV Previously treated Ph + CML Monotherapy Diarrhea, rash, liver enzyme elevations Active, not recruiting
NCT03106779 III CML Bosutinib vs. ABL001 Recruiting
NCT01331291 II Glioblastoma Monotherapy Completed
NCT00319254 II Breast cancer Monotherapy Completed
NCT03023319 I Metastatic solid tumors + Pemetrexed Recruiting
Gilteritinib (ASP2215) Astellas Pharma/Kotobuki Pharmaceutical FLT3, AXL IC50 (in vitro) = 0.73 nM NCT02927262 III Relapsed or treatment refractory FLT3 mutated AML Gilteritinib or placebo Febrile neutropenia, anemia, thrombocytopenia, sepsis, pneumonia, diarrhea, fatigue, elevated aspartate aminotransferase and alanine aminotransferase Recruiting
NCT02456883 I Advanced solid tumors Monotherapy Completed
NCT02495233 I/II NSCLC + Erlotinib Terminated
S49076 Servier MET, MER, AXL FGFR3 IC50 (in vitro) = 7 nM IC50 (in cells) = 56 nM ISRCTN00759419 I Advanced solid tumors Monotherapy Peripheral oedema and hypoalbuminaemia Completed
Amuvatinib (MP-470) Astex Pharmaceuticals KIT, AXL, PDGFR1, FLT3, RET IC50 (in vitro) = 10 nM NCT01357395 II SCLC Monotherapy Fatigue, alopecia, diarrhea, nausea, anorexia, neutropenia, anemia, thrombocytopenia, leukopenia Completed
NCT00894894 I Solid tumors Monotherapy Completed
NCT00504205 Not Applicable Unresectable or metastatic solid tumor or lymphoma Monotherapy Terminated
Sunitinib (SU11248, marketed as Sutent) Pfizer PDGFR, VEGFR2, FLT3, KIT, AXL IC50 (in vitro) = 5 nM NCT00706706 IV Metastatic RCC Monotherapy Diarrhea, fatigue, hypertension, palmar-plantar erythrodysesthesia, and hematologic adverse events Completed
NCT02691793 IV Refractory Solid Tumors Monotherapy Recruiting
NCT01525550 IV Pancreatic neuroendocrine tumor Monotherapy Completed
NCT00793871 IV GIST Monotherapy Completed
NCT00794950 II Urothelial carcinoma Monotherapy Active, not recruiting
NCT01718327 II Unresectable and advanced cholangiocarcinoma Monotherapy   Completed
NCT01824615 II Ovarian cancer Monotherapy   Completed
NCT02623127 II Thymic carcinoma Monotherapy   Completed
NCT00372775 II NSCLC Monotherapy   Completed
NCT01498835 I Soft tissue sarcoma Monotherapy   Completed
SNS314 2-D08 Sunesis Pharmaceuticals Aurora A/B/C, Trk A/B, FLT4, Fms, Axl IC50 (in vitro) = 84 nM NCT00519662 I advanced solid tumors Monotherapy Not reported Completed
AXL, IRAK4, ROS1 IC50 (in vitro) = 0.49 nM Preclinical
UNC2025 University of North Carolina MER, FLT3, AXL, Tyro3 IC50 (in vitro) = 14 nM Preclinical
SGI-7079 Tolero Pharmaceuticals/Astex Pharmaceuticals AXL (selective) IC50 (in vitro) = 58 nM IC50 (in vivo) < 1 uM Preclinical
UNC569   MER, AXL, Tyro3 IC50 (in vitro) = 37 nM Preclinical
NA80x1   AXL (selective) IC50 (in vitro) = 12.67 ± 0.45 μM, IC50 (in vivo) = 4.11 ± 1.47uM Preclinical
DP-3975 Deciphera Pharmaceuticals, LLC AXL (selective) IC50 (in vitro) = 100 nM  2 uM Preclinical
  1. Abbreviations: NSCLC non-small cell lung cancer, TNBC triple-negative breast cancer, AML acute myeloid leukemia, MDS myelodysplastic syndrome, CLL chronic lymphocytic leukemia, CML chronic myelogenous leukemia, FLT3 FMS-like tyrosine kinase 3, GIST gastrointestinal stromal tumors, RCC renal cell carcinoma, SCLC small cell lung cancer
  2. aIn the order of inhibition potency
  3. bAll the relevant information of clinical trials can be found on the public clinical trial registry website (clinicaltrials.gov). Here is a partial list of all the relevant clinical trials