Novel small molecule multi-kinase inhibitors currently undergoing clinical investigation in chronic myeloid leukemia.
| Drug name . | Sponsor . | Histologies under investigation . | Potential drug targets . | Hematology clinical trial registration . |
|---|---|---|---|---|
| *Clinical or laboratory activity against the T315I mutation; (c) completed clinical trial; (t) terminated clinical trial | ||||
| ABL indicates Bcr-Abl (Abelson) kinase; SFK, Src family kinase; KIT, CD117; TEC, Tec protein kinase; STE20, serine/threonine 20 kinase; CAMK2G, calcium/calmodulin-dependent protein kinase (CaM kinase) II gamma kinase; PDGFR, platelet-derived growth factor receptor; FGFR1, fibroblast growth factor receptor 1; IGF1R, insulin like growth factor receptor; JAK, Janus kinase; FLT3, fms-like tyrosine kinase receptor-3; RET, rearranged during transfection kinase; TRK, tropomyosin-receptor-kinase; MCL-1, myeloid cell leukemia sequence 1; TIE2, tyrosine kinase with immunoglobulin-like and EGF-like domains 2; KDR, kinase insert domain receptor A gene. | ||||
| Approved Agents | ||||
| Dasatinib | BMS | ABL, KIT, PDGFR, SFK | FDA approved | |
| Nilotinib | Novartis | ABL, KIT, PDGFR | FDA Approved | |
| Investigational Agents | ||||
| Bosutinib | Wyeth | CML, breast cancer | ABL, CAMK2G SFK, STE20, TEC | Phase I/II/III NCT00574873 NCT00261846 INNO-406 |
| (NS-187) | CytRx | CML, Ph+ ALL | ABL, KIT, LYN, PDGFR | Phase I/II NCT00352677 (c) |
| AP24534* | Ariad | CML, advanced hematologic malignancies | ABL, FGFR1, FLT3, KIT, VEGFR | Phase I NCT00660920 |
| XL228* | Exelixis | CML, Ph+ ALL, lymphoma, myeloma, solid tumors | ABL, Aurora A, FGFR1–3, IGF1R, SRC | Phase I NCT00464113 |
| AT9283 | Astex Therapeutics | CML, AML, ALL, MDS, myelofibrosis, NHL, solid cancers | ABL, Aurora A&B, FLT3, JAK2, JAK3 | Phase I/II NCT00522990 |
| PHA739358* | Nerviano Medical Sciences | CML, myeloma, prostate | ABL, Aurora A&B, FGFR1, RET, TRK | Phase II NCT00335868 |
| KW-2449* | Kyowa Hakko Kirin Pharma | CML, AML | ABL, Aurora A, FGFR1, FLT3 | Phase I NCT00346632(t) Phase I/II NCT00779480 |
| MK-0457* | Merck | CML, ALL, MDS | ABL, Aurora A&B, FLT3, JAK2 | Phase I/II NCT00111683(c) |
| Homoharringtonine (HHT)* | ChemGenex | CML | cytochrome C, MCL-1 | Phase II NCT00375219 NCT00462943 NCT00114959 (c) |
| DCC2036* | Deciphera | CML, Ph+ ALL | ABL, FLT3, KDR SFK, TIE2 | Phase I NCT00827138 |
| Drug name . | Sponsor . | Histologies under investigation . | Potential drug targets . | Hematology clinical trial registration . |
|---|---|---|---|---|
| *Clinical or laboratory activity against the T315I mutation; (c) completed clinical trial; (t) terminated clinical trial | ||||
| ABL indicates Bcr-Abl (Abelson) kinase; SFK, Src family kinase; KIT, CD117; TEC, Tec protein kinase; STE20, serine/threonine 20 kinase; CAMK2G, calcium/calmodulin-dependent protein kinase (CaM kinase) II gamma kinase; PDGFR, platelet-derived growth factor receptor; FGFR1, fibroblast growth factor receptor 1; IGF1R, insulin like growth factor receptor; JAK, Janus kinase; FLT3, fms-like tyrosine kinase receptor-3; RET, rearranged during transfection kinase; TRK, tropomyosin-receptor-kinase; MCL-1, myeloid cell leukemia sequence 1; TIE2, tyrosine kinase with immunoglobulin-like and EGF-like domains 2; KDR, kinase insert domain receptor A gene. | ||||
| Approved Agents | ||||
| Dasatinib | BMS | ABL, KIT, PDGFR, SFK | FDA approved | |
| Nilotinib | Novartis | ABL, KIT, PDGFR | FDA Approved | |
| Investigational Agents | ||||
| Bosutinib | Wyeth | CML, breast cancer | ABL, CAMK2G SFK, STE20, TEC | Phase I/II/III NCT00574873 NCT00261846 INNO-406 |
| (NS-187) | CytRx | CML, Ph+ ALL | ABL, KIT, LYN, PDGFR | Phase I/II NCT00352677 (c) |
| AP24534* | Ariad | CML, advanced hematologic malignancies | ABL, FGFR1, FLT3, KIT, VEGFR | Phase I NCT00660920 |
| XL228* | Exelixis | CML, Ph+ ALL, lymphoma, myeloma, solid tumors | ABL, Aurora A, FGFR1–3, IGF1R, SRC | Phase I NCT00464113 |
| AT9283 | Astex Therapeutics | CML, AML, ALL, MDS, myelofibrosis, NHL, solid cancers | ABL, Aurora A&B, FLT3, JAK2, JAK3 | Phase I/II NCT00522990 |
| PHA739358* | Nerviano Medical Sciences | CML, myeloma, prostate | ABL, Aurora A&B, FGFR1, RET, TRK | Phase II NCT00335868 |
| KW-2449* | Kyowa Hakko Kirin Pharma | CML, AML | ABL, Aurora A, FGFR1, FLT3 | Phase I NCT00346632(t) Phase I/II NCT00779480 |
| MK-0457* | Merck | CML, ALL, MDS | ABL, Aurora A&B, FLT3, JAK2 | Phase I/II NCT00111683(c) |
| Homoharringtonine (HHT)* | ChemGenex | CML | cytochrome C, MCL-1 | Phase II NCT00375219 NCT00462943 NCT00114959 (c) |
| DCC2036* | Deciphera | CML, Ph+ ALL | ABL, FLT3, KDR SFK, TIE2 | Phase I NCT00827138 |