Dual Kinase Targeting in Leukemia
Abstract
:Simple Summary
Abstract
1. Introduction
1.1. Dual Kinase Targeting in AML
1.2. Dual Kinase Targeting in CML
1.3. Dual Kinase Targeting in Lymphoid Tumors
1.4. Other Dual Activity Inhibitors in Leukemia
1.5. PROTACs
2. Conclusions
Funding
Conflicts of Interest
References
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Compound | Targets | Disease | Status | Clinical Trials | Ref. |
---|---|---|---|---|---|
OSI-027 | mTORC1 mTORC2 | AML | Phase 1 | NCT00698243 (5% SD) | [31,32,33] |
AZD8055 | mTORC1 mTORC2 | Solid and hematologic | Discontinued | NCT00731263 (18% SD) | [34,35] |
AZD2014/Vistusertib | mTORC1 mTORC2 | DLBCL | Phase 2 | NCT02752204 | [38,39] |
TAK-228/MLN0128 | mTORC1 mTORC2 | Lymphoma | Phase 1/2 | NCT02727777 | [42,43] |
PP242 | mTORC1 mTORC2 | AML | Preclinical | - | [40] |
PI-103 | PI3K mTOR | AML, ALL | Preclinical | - | [47,87] |
Dactolisib | PI3K mTOR | AML, ALL, FL | Phase 1 | NCT01756118 (30% ORR) | [50,51,52,88,89,90,91,92] |
NVP-BGT226 | PI3K mTOR | AML | Preclinical | - | [51] |
SEL24-B489 | PIM1 FLT3 | AML | Phase 1/2 | NCT03008187 | [58] |
SGI-1776 | PIM1 FLT3 | AML | Discontinued | NCT01239108 | [60] |
Pacritinib | FLT3 JAK2 | AML | Phase 2 | NCT02323607 (23–50% CR) NCT02532010 | [66,67] |
Crenolanib | PDGF FLT3 | AML | Phase 3 | NCT01657682 NCT03250338 | [68,69] |
TAK-659 | SYK FLT3 | AML | Phase 1/2 | NCT02323113 | [72] |
CCT137690 | Aurora FLT3 | AML | Preclinical | - | [73,74] |
CCT241736 | Aurora FLT3 | AML | Preclinical | - | [74,75] |
Ilorasertib | Aurora VEGFR FLT3 | AML | Phase 1 | NCT01110473 (8% ORR) | [76,77] |
AMG-925 | FLT3 CDK4 | AML | Preclinical | - | [78] |
Gilteritinib | FLT3 AXL | AML | Approved | NCT02421939 (28% CR) | [84,86] |
Compound | Targets | Disease | Status | Clinical Trials | Refs |
---|---|---|---|---|---|
ON123300 | PI3K CDK4/6 | MCL | Preclinical | - | [133] |
PHA-767491 | CDC7 CDK9 | CLL, MM | Preclinical | - | [134,135,136,137,138,139] |
Cerdulatinib | SYK JAK | CLL, FL | Phase 1 | NCT01994382 (30–38% ORR) | [142,143,144,145,146] |
Duvelisib | PI3K-δ PI3K-γ | CLL, NHL, FL | Approved | NCT01882803 (47% ORR) | [148,149,150,151] |
NCT02004522 (74% ORR) | |||||
NCT01476657 (56–83% ORR) | |||||
PI3KD/V-IN-01 | PI3K-δ PIK3C3 | AML, CLL, Burkitt’s lymphoma | Preclinical | - | [152] |
Umbralisib | PI3K-δ CK1ε | CLL, NHL | Phase 1 | NCT01767766 (37% ORR) | [153,154,155] |
Bimiralisib | PI3K mTOR | Lymphoma | Phase 1/2 | NCT03127020 (73% ORR) | [158,159] |
Gedatolisib | PI3K-α mTOR | ALL | Preclinical | - | [160,161] |
CC-115 | mTOR DNA-PK | CLL | Phase 1 | NCT01353625 38% PR, 25% SD | [162,163] |
NVP-BAG956 | PI3K PDK1 | ALL | Preclinical | - | [164] |
QL-X-138 | BTK MNK | B-cell lymphoma | Preclinical | - | [165] |
Compound | Targets | Disease | Refs |
---|---|---|---|
YKL-06-101 | CDK8 mTOR | ALL | [192] |
SIAIS178 | BCR/ABL | CML | [194] |
GMB-475 | BCR/ABL | CML | [195] |
MT-802 | BTK | CLL | [196] |
YX-2-107 | CDK6 | ALL | [197] |
FLT-PROTAC | FLT3 | AML | [198] |
HBL-4 | BRD4 PLK1PLK1 | AML | [199] |
MS4078 | ALK | ALCL | [200] |
TD-004 | ALK | ALCL | [201] |
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Mologni, L.; Marzaro, G.; Redaelli, S.; Zambon, A. Dual Kinase Targeting in Leukemia. Cancers 2021, 13, 119. https://doi.org/10.3390/cancers13010119
Mologni L, Marzaro G, Redaelli S, Zambon A. Dual Kinase Targeting in Leukemia. Cancers. 2021; 13(1):119. https://doi.org/10.3390/cancers13010119
Chicago/Turabian StyleMologni, Luca, Giovanni Marzaro, Sara Redaelli, and Alfonso Zambon. 2021. "Dual Kinase Targeting in Leukemia" Cancers 13, no. 1: 119. https://doi.org/10.3390/cancers13010119
APA StyleMologni, L., Marzaro, G., Redaelli, S., & Zambon, A. (2021). Dual Kinase Targeting in Leukemia. Cancers, 13(1), 119. https://doi.org/10.3390/cancers13010119