Pair Name | Homoharringtonine, ACC010 | ||
Phytochemical Name | Homoharringtonine (PubChem CID: 285033 ) | ||
Anticancer drug Name | ACC010 (PubChem CID: / ) | ||
Structure of Phytochemical |
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2D
MOL
3D
MOL
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Structure of Anticancer Drug |
Download
2D
MOL
3D
MOL
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Pair Name | Homoharringtonine, ACC010 | |||
Disease Info | [ICD-11: 2A60.Z] | Acute myeloid leukemia | Investigative | |
Biological Phenomena | Induction-->Apoptosis | |||
Gene Regulation | Down-regulation | Phosphorylation | AKT1 | hsa207 |
Up-regulation | Cleavage | CASP3 | hsa836 | |
Up-regulation | Cleavage | CASP7 | hsa840 | |
Down-regulation | Expression | CDK2 | hsa1017 | |
Down-regulation | Expression | CDK4 | hsa1019 | |
Down-regulation | Expression | CDK6 | hsa1021 | |
Up-regulation | Expression | CDKN1A | hsa1026 | |
Down-regulation | Phosphorylation | FLT3 | hsa2322 | |
Down-regulation | Expression | MYC | hsa4609 | |
Up-regulation | Cleavage | PARP1 | hsa142 | |
Up-regulation | Expression | PSMD9 | hsa5715 | |
Down-regulation | Phosphorylation | RB1 | hsa5925 | |
Down-regulation | Phosphorylation | STAT5 | hsa6776 | |
In Vitro Model | MV4‐11 | Childhood acute monocytic leukemia | Homo sapiens (Human) | CVCL_0064 |
MOLM-13 | Adult acute myeloid leukemia | Homo sapiens (Human) | CVCL_2119 | |
In Vivo Model | MOLM13‐luciferase cells (1×10⁶) were injected into each mouse via the tail vein. After 6 days, cell engraftment was assessed after intraperitoneal injection of luciferin. | |||
Result | ACC010 and HHT cooperatively downregulated MYC and inhibited FLT3 activation. Further, when HHT was added, ACC010-resistant cells demonstrated a good synergy. We also extended our study to the mouse BaF3 cell line with FLT3-inhibitor-resistant FLT3-ITD/tyrosine kinase domain mutations and AML cells without FLT3-ITD. Collectively, our results suggested that the combination treatment of ACC010 and HHT might be a promising strategy for AML patients, especially those carrying FLT3-ITD. |
No. | Title | Href |
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1 | ACC010, a novel BRD4 inhibitor, synergized with homoharringtonine in acute myeloid leukemia with FLT3-ITD. Mol Oncol. 2023 Jul;17(7):1402-1418. doi: 10.1002/1878-0261.13368. | Click |