US12129258, Example Crizotinib BDBM50306682 US10370379, Crizotinib (R)-3-(1-(2,6-dichloro-3-fluorophenyl)ethoxy)-5-(1-(piperidin-4-yl)-1H-pyrazol-4-yl)pyridin-2-amine CHEMBL601719 US11059827, Compound Crizotinib US9199944, Crizotinib PF-2341066 3-[(1R)-1-(2,6-dichloro-3-fluorophenyl)ethoxy]-5-(1-piperidin-4-yl-1H-pyrazol-4-yl)pyridin-2-amine US10543199, Compound Crizotinib US9126941, PF-2341066 US11517561, Compound Crizotinib CRIZOTINIB 3-(2,6-dichloro-3-fluorobenzyloxy)-5-(1-(piperidin-4-yl)-1H-pyrazol-4-yl)pyridin-2-amine US10780082, Compound Crizotinib US9226923, Crizotinib
PONATINIB BDBM50322535 US9255107, AP24534 US10464902, Ponatinib 3-[2-(Imidazo[1,2-b]pyridazin-3-yl)ethynyl]-4-methyl-N-{4-[(4-methylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl}benzamide CHEMBL1171837 3-(imidazo[1,2-b]pyridazin-3-ylethynyl)-4-methyl-N-{4-[(4-methylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl}benzamide
- Liu, Y; Peng, X; Guan, X; Lu, D; Xi, Y; Jin, S; Chen, H; Zeng, L; Ai, J; Geng, M; Hu, Y Discovery of novel Ponatinib analogues for reducing KDR activity as potent FGFRs inhibitors. Eur J Med Chem 126: 122-132 (2017)
- Kaiser, TM; Dentmon, ZW; Dalloul, CE; Sharma, SK; Liotta, DC Accelerated Discovery of Novel Ponatinib Analogs with Improved Properties for the Treatment of Parkinson's Disease. ACS Med Chem Lett 11: 491-496 (2020)
- Lim, JW; Kim, SK; Choi, SY; Kim, DH; Gadhe, CG; Lee, HN; Kim, HJ; Kim, J; Cho, SJ; Hwang, H; Seong, J; Jeong, KS; Lee, JY; Lim, SM; Lee, JW; Pae, AN Identification of crizotinib derivatives as potent SHIP2 inhibitors for the treatment of Alzheimer's disease. Eur J Med Chem 157: 405-422 (2018)
- Liu, X; Zhang, L; Wan, H; Zhu, Z; Jin, J; Qin, Y; Mao, W; Yan, K; Fang, D; Jiang, W; Hu, L; Chen, J; Chen, K; Chen, S; Li, J; Zhao, S; Zheng, S; Zhang, L; Ding, CZ Discovery and preclinical evaluations of WX-0593, a novel ALK inhibitor targeting crizotinib-resistant mutations. Bioorg Med Chem Lett 66: (2022)
- Huang, Q; Johnson, TW; Bailey, S; Brooun, A; Bunker, KD; Burke, BJ; Collins, MR; Cook, AS; Cui, JJ; Dack, KN; Deal, JG; Deng, YL; Dinh, D; Engstrom, LD; He, M; Hoffman, J; Hoffman, RL; Johnson, PS; Kania, RS; Lam, H; Lam, JL; Le, PT; Li, Q; Lingardo, L; Liu, W; Lu, MW; McTigue, M; Palmer, CL; Richardson, PF; Sach, NW; Shen, H; Smeal, T; Smith, GL; Stewart, AE; Timofeevski, S; Tsaparikos, K; Wang, H; Zhu, H; Zhu, J; Zou, HY; Edwards, MP Design of potent and selective inhibitors to overcome clinical anaplastic lymphoma kinase mutations resistant to crizotinib. J Med Chem 57: 1170-87 (2014)
- Mathi, GR; Kang, CH; Lee, HK; Achary, R; Lee, HY; Lee, JY; Ha, JD; Ahn, S; Park, CH; Lee, CO; Hwang, JY; Yun, CS; Jung, HJ; Cho, SY; Kim, HR; Kim, P Replacing the terminal piperidine in ceritinib with aliphatic amines confers activities against crizotinib-resistant mutants including G1202R. Eur J Med Chem 126: 536-549 (2017)
- Chen, W; Guo, X; Zhang, C; Ke, D; Zhang, G; Yu, Y Discovery of 2-aminopyridines bearing a pyridone moiety as potent ALK inhibitors to overcome the crizotinib-resistant mutants. Eur J Med Chem 183: (2019)
- Wang, Y; Chen, S; Hu, G; Wang, J; Gou, W; Zuo, D; Gu, Y; Gong, P; Zhai, X Discovery of novel 2,4-diarylaminopyrimidine analogues as ALK and ROS1 dual inhibitors to overcome crizotinib-resistant mutants including G1202R. Eur J Med Chem 143: 123-136 (2018)
- Zou, HY; Li, Q; Engstrom, LD; West, M; Appleman, V; Wong, KA; McTigue, M; Deng, YL; Liu, W; Brooun, A; Timofeevski, S; McDonnell, SR; Jiang, P; Falk, MD; Lappin, PB; Affolter, T; Nichols, T; Hu, W; Lam, J; Johnson, TW; Smeal, T; Charest, A; Fantin, VR PF-06463922 is a potent and selective next-generation ROS1/ALK inhibitor capable of blocking crizotinib-resistant ROS1 mutations. Proc Natl Acad Sci U S A 112: 3493-8
- Liu, S; Jiang, Y; Yan, R; Li, Z; Wan, S; Zhang, T; Wu, X; Hou, J; Zhu, Z; Tian, Y; Zhang, J Design, synthesis and biological evaluations of 2-amino-4-(1-piperidine) pyridine derivatives as novel anti crizotinib-resistant ALK/ROS1 dual inhibitors. Eur J Med Chem 179: 358-375 (2019)
- Johnson, TW; Gallego, RA; Brooun, A; Gehlhaar, D; McTigue, M Reviving B-Factors: Retrospective Normalized B-Factor Analysis of c-ros Oncogene 1 Receptor Tyrosine Kinase and Anaplastic Lymphoma Kinase L1196M with Crizotinib and Lorlatinib. ACS Med Chem Lett 9: 878-883 (2018)
- Cui, JJ; Tran-Dubé, M; Shen, H; Nambu, M; Kung, PP; Pairish, M; Jia, L; Meng, J; Funk, L; Botrous, I; McTigue, M; Grodsky, N; Ryan, K; Padrique, E; Alton, G; Timofeevski, S; Yamazaki, S; Li, Q; Zou, H; Christensen, J; Mroczkowski, B; Bender, S; Kania, RS; Edwards, MP Structure based drug design of crizotinib (PF-02341066), a potent and selective dual inhibitor of mesenchymal-epithelial transition factor (c-MET) kinase and anaplastic lymphoma kinase (ALK). J Med Chem 54: 6342-63 (2011)
- ChEMBL_2362670 Inhibition of wild type human BCR-ABL1 using Tyr2 peptide as substrate incubated for 1 hrs in presence of ponatinib by FRET based Z-LYTE assay
- ChEMBL_2362673 Inhibition of human BCR-ABL1 T315I mutant using Tyr2 peptide as substrate incubated for 1 hrs in presence of ponatinib by FRET based Z-LYTE assay
- ChEMBL_2060935 (CHEMBL4716188) Inhibition of crizotinib-resistant ALK G1202R mutant (unknown origin) using peptide substrate incubated for 30 mins in presence of ATP by fluorescence assay
- ChEMBL_2060936 (CHEMBL4716189) Inhibition of crizotinib-resistant ALK L1196M mutant (unknown origin) using peptide substrate incubated for 30 mins in presence of ATP by fluorescence assay
- ChEMBL_2060937 (CHEMBL4716190) Inhibition of crizotinib-resistant ALK G1269A mutant (unknown origin) using peptide substrate incubated for 30 mins in presence of ATP by fluorescence assay
- ChEMBL_2060939 (CHEMBL4716192) Inhibition of crizotinib-resistant ALK F1174L mutant (unknown origin) using peptide substrate incubated for 30 mins in presence of ATP by fluorescence assay
- ChEMBL_2060940 (CHEMBL4716193) Inhibition of crizotinib-resistant ALK C1156Y mutant (unknown origin) using peptide substrate incubated for 30 mins in presence of ATP by fluorescence assay
- Inhibitory Activity of Compounds on TRKA and ALK-L1196M Based on HTRF of Cisbio (Cisbio, Cat. 08-52) principle, TRKA and ALK-L1196M kinase activity detection platform were established to determine the inhibitory activity of compounds. The compound powder was dissolved in 100% DMSO (Sigma, Cat. D8418-11) to prepare a 10 mM storage solution. The compounds had an initial test concentration of 1000 nM and 10,000 nM respectively, were 3-fold serially diluted to obtain 11 samples for multiple hole inspection. RXDX-101 (WuXi AppTec. supplied) or Crizotinib (WuXi AppTec. Supplied) was used as positive reference compound.The gradient diluted compounds were mixed with 0.5 nM TRKA (Carna, Cat. 08-186)/ALK-L1196M (Carna, Cat. 08-529), 0.3 μM/1 μM TK Substrate-biotin and 90 μM/30 μM ATP (Sigma, Cat. A7699) in a Optiplate-384F plate (PerkinElmer, Cat. 6007299) and incubated at room temperature for 90 mins/120 mins. Then 0.67 nM Eu-TK-Antibody and 50 nM Streptavidin-XL-665 were added, mixed and incubated at room temperature for 60 min. The fluorescence value was obtained by Envision (PerkinElmer, #2014) (Excitation light, 320 nm; Emission light, 665 nm). The IC50 values of the compounds were calculated using XLFIT5 (IDBS) software.