TKIs, their indications, and the (off-target) kinases they inhibit
| Class/drugs . | Indication (T)rial/(R)egistration/(O)ff-label . | Relevant immunomodulatory off-target molecules . |
|---|---|---|
| BTK* | ||
| Ibrutinib | CLL/SLL(R), WM(R), MCL(R), MZL(R), BCL(R), cGvHD(R)103 | ITK, EGFR, JAK3103 |
| Acalabrutinib | CLL/SLL(R), NHL(R), MCL(R)104 | |
| Zanubrutinib | MZL(R), CLL/SLL(T), WM(T), MCL(T)105 | |
| Tirabrutinib | CLL(T), BCL(T), WM(T), PCNSL(T)104 | |
| SYK† | ||
| Fostamatinib | ITP(R), RA(T), CLL(T), BCL(T)106,107 | FLT3, JAK263,108 |
| Entospletinib | AML(T), CLL(T), BCL(T), GvHD(T), MCL(T), NHL(T)106 | JAK2106 |
| Cerdulatinib | DLBCL(T), CLL(T), NHL(T)106 | JAK1/JAK3, AKT, NF-κB106,107 |
| BCR-Abl‡ | ||
| Imatinib | Ph+CML(R)109 | |
| Nilotinib | Ph+CML(R)110 | |
| Dasatinib | Ph+CML(R)58 | BTK58 |
| Bosutinib | Ph+CML(R), Ph+ALL(R)111 | |
| Ponatinib | Ph+CML(R), Ph+ALL(R)111 | Abl, FLT3111 |
| Radotinib | Ph+CML(R)112 | |
| PI3K/mTOR§ | ||
| Idelalisib (p110δ) | ALL(R), CLL/SLL(R), FL(R)113 | |
| Copanlisib (PI3Kδ & PI3Kδ) | FL(R), CLL/SLL(R)114,115 | |
| Duvelisib | FL(R), CLL/SLL(R)115 | |
| Umbralisib (PI3Kδ) | MZL(T), CLL(T), FL(T), DLBCL(T)116 | |
| Temsirolimus | NHL(R), MCL(R).117 | |
| JAK¶ | ||
| Ruxolitinib (JAK1/2) | PV(R), MF(R), GvHD(R)118 | |
| Fedratinib (JAK2) | MF(R)119 | FLT3, BCR-Abl120 |
| Momelotinib (JAK1/2) | MPN(T)121 | |
| Pacritinib (JAK2) | MPN(T)122 | FLT3122 |
| FLT3|| | ||
| Midostaurin | FLT3-mutated AML(R), ASM(R), MC(R)123 | SYK123 |
| Sunitinib | RCC(R), GI(R), FLT3-mutated AML(O)124 | |
| Sorafenib | HCC(R), RCC(R), FLT3-mutated AML(O)125 | |
| Gilteritinib | FLT3-mutated AML(R)125 | |
| Crenolanib | FLT3-mutated AML(T)125 | |
| Quizartinib | FLT3-mutated AML(T)125 |
| Class/drugs . | Indication (T)rial/(R)egistration/(O)ff-label . | Relevant immunomodulatory off-target molecules . |
|---|---|---|
| BTK* | ||
| Ibrutinib | CLL/SLL(R), WM(R), MCL(R), MZL(R), BCL(R), cGvHD(R)103 | ITK, EGFR, JAK3103 |
| Acalabrutinib | CLL/SLL(R), NHL(R), MCL(R)104 | |
| Zanubrutinib | MZL(R), CLL/SLL(T), WM(T), MCL(T)105 | |
| Tirabrutinib | CLL(T), BCL(T), WM(T), PCNSL(T)104 | |
| SYK† | ||
| Fostamatinib | ITP(R), RA(T), CLL(T), BCL(T)106,107 | FLT3, JAK263,108 |
| Entospletinib | AML(T), CLL(T), BCL(T), GvHD(T), MCL(T), NHL(T)106 | JAK2106 |
| Cerdulatinib | DLBCL(T), CLL(T), NHL(T)106 | JAK1/JAK3, AKT, NF-κB106,107 |
| BCR-Abl‡ | ||
| Imatinib | Ph+CML(R)109 | |
| Nilotinib | Ph+CML(R)110 | |
| Dasatinib | Ph+CML(R)58 | BTK58 |
| Bosutinib | Ph+CML(R), Ph+ALL(R)111 | |
| Ponatinib | Ph+CML(R), Ph+ALL(R)111 | Abl, FLT3111 |
| Radotinib | Ph+CML(R)112 | |
| PI3K/mTOR§ | ||
| Idelalisib (p110δ) | ALL(R), CLL/SLL(R), FL(R)113 | |
| Copanlisib (PI3Kδ & PI3Kδ) | FL(R), CLL/SLL(R)114,115 | |
| Duvelisib | FL(R), CLL/SLL(R)115 | |
| Umbralisib (PI3Kδ) | MZL(T), CLL(T), FL(T), DLBCL(T)116 | |
| Temsirolimus | NHL(R), MCL(R).117 | |
| JAK¶ | ||
| Ruxolitinib (JAK1/2) | PV(R), MF(R), GvHD(R)118 | |
| Fedratinib (JAK2) | MF(R)119 | FLT3, BCR-Abl120 |
| Momelotinib (JAK1/2) | MPN(T)121 | |
| Pacritinib (JAK2) | MPN(T)122 | FLT3122 |
| FLT3|| | ||
| Midostaurin | FLT3-mutated AML(R), ASM(R), MC(R)123 | SYK123 |
| Sunitinib | RCC(R), GI(R), FLT3-mutated AML(O)124 | |
| Sorafenib | HCC(R), RCC(R), FLT3-mutated AML(O)125 | |
| Gilteritinib | FLT3-mutated AML(R)125 | |
| Crenolanib | FLT3-mutated AML(T)125 | |
| Quizartinib | FLT3-mutated AML(T)125 |
AKT, protein kinase B; ALL, acute lymphoid leukemia; AML, acute myeloid leukemia; ASM, aggressive systemic mastocytosis; BCL, B-cell lymphoma; cGvHD, chronic graft-versus-host disease; CLL, chronic lymphocytic leukemia; CML, chronic myeloid leukemia; DLBCL, diffuse large B-cell lymphoma; EGFR, epidermal growth factor receptor; FL, follicular non-Hodgkin lymphoma; GI, gastrointestinal tumors; GvHD, graft-versus-host disease; HCC, hepatocellular carcinoma; ITP, idiopathic thrombocytopenic purpura; ITK, interleukin-2–inducible T-cell kinase; MC, mast cell leukemia; MCL, mantle cell lymphoma; MF, myelofibrosis; MPN, myeloproliferative neoplasm; MZL, marginal zone lymphoma; NHL, non-Hodgkin lymphoma; PCSNL, primary central nervous system lymphoma; Ph+, Philadelphia chromosome positive; PV, polycythemia vera; RA, rheumatoid arthritis; RCC, renal cell carcinoma; SLL, small lymphocytic leukemia; WM, Waldenström macroglobulinemia.
Summarized in supplemental Table 1.
Summarized in supplemental Table 2.
Summarized in supplemental Table 3.
Summarized in supplemental Table 4.
Summarized in supplemental Table 5.
Summarized in supplemental Table 6.