| Identification | Back Directory | [Name]
H3B-8800
(H3B8800) | [CAS]
1825302-42-8 | [Synonyms]
H3B-8800
(H3B8800)
1-Piperazinecarboxylic acid, 4-methyl-, (2S,3S,4E,6S,7R,10R)-7,10-dihydroxy-3,7-dimethyl-2-[(1E,3E,5R)-1-methyl-5-(2-pyridinyl)-1,3-hexadien-1-yl]-12-oxooxacyclododec-4-en-6-yl ester | [Molecular Formula]
C31H45N3O6 | [MOL File]
1825302-42-8.mol | [Molecular Weight]
555.71 |
| Chemical Properties | Back Directory | [Boiling point ]
710.6±60.0 °C(Predicted) | [density ]
1.19±0.1 g/cm3(Predicted) | [solubility ]
DMSO: Slightly soluble: 0.1-1 mg/ml
Ethanol: Slightly soluble: 0.1-1 mg/ml | [form ]
Solid | [pka]
13.92±0.70(Predicted) | [color ]
Yellow to orange | [InChIKey]
YOIQWBAHJZGRFW-WVRLKXNASA-N | [SMILES]
N1(C(O[C@@H]2[C@@](O)(C)CC[C@@H](O)CC(=O)O[C@H](/C(/C)=C/C=C/[C@H](C3=NC=CC=C3)C)[C@@H](C)C=C2)=O)CCN(C)CC1 |t:32| |
| Hazard Information | Back Directory | [Uses]
H3B-8800 is a potent and orally active SF3B splicing modulator. H3B-8800 direct interaction with the SF3b complex and shows anti-cancer activity. H3B-8800 has the potential for the research of acute myeloid leukemia (AML) with SF3B1 mutant[1]. | [in vivo]
H3B-8800 (2, 4 mg/kg; p.o.; daily) shows anti tumor activity in AML derived xenografts (PDXs) with a mutation in SF3B1[1]. | Animal Model: | 6-8 weeks, female NSG or CB17-SCID mice (K562 cells with SF3B1WT or SF3B1K700E)[1] | | Dosage: | 2, 4 mg/kg | | Administration: | P.o.; daily | | Result: | Resulted in antileukemic efficacy and splicing modulation in mice bearing AML patient-derived xenografts (PDXs) with a mutation in SF3B1 but had little effect in mice bearing SF3B1WT AML PDXs, significantly reduced leukemic burden relative in SF3B1K700E PDX. |
| [References]
[1] Seiler M, et al. H3B-8800, an orally available small-molecule splicing modulator, induces lethality in spliceosome-mutant cancers. Nat Med. 2018 May;24(4):497-504. DOI:10.1038/nm.4493 |
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