76958-67-3

76958-67-3 structure

Name: Hypothemycin
Chemical Name: hypothemycin
CAS Number: 76958-67-3
Molecular Formula: C₁₉H₂₂O₈
Molecular Weight: 378.37300
Catalog: Signaling Pathways MAPK/ERK Pathway ERK
Create Date: 2016-12-27 19:36:19
Modify Date: 2024-01-02 10:50:22
Hypothemycin, a fungal polyketide, is a multikinase inhibitor with Kis of 10/70 nM, 17/38 nM, 90 nM, 900 nM/1.5 μM, and 8.4/2.4 μM for VEGFR2/VEGFR1, MEK1/MEK2, FLT-3, PDGFRβ/PDGFRα, and ERK1/ERK2, respectively[1][2].

Name	hypothemycin
Synonyms	(1aR,3S,4S,6Z,9S,15bR)-1a,8,9,15b-Tetrahydro-3,4,12-trihydroxy-9-methyl-14-methoxy-3H-oxireno[k][2]benzoxacyclotetradecin-5,11(2H,4H)-dione MFCD08457932 Hypothemicin (1aR,3S,4S,6Z,9S,15bR)-1a,2,4,5,11,8,9,15b-Octahydro-3,4,12-trihydroxy-9-methyl-14-methoxy-3H-oxireno[k][2]benzoxacyclotetradecin-5,11-dione

Description	Hypothemycin, a fungal polyketide, is a multikinase inhibitor with Kis of 10/70 nM, 17/38 nM, 90 nM, 900 nM/1.5 μM, and 8.4/2.4 μM for VEGFR2/VEGFR1, MEK1/MEK2, FLT-3, PDGFRβ/PDGFRα, and ERK1/ERK2, respectively[1][2].
Related Catalog	Research Areas >> Cancer Signaling Pathways >> MAPK/ERK Pathway >> MEK Signaling Pathways >> Protein Tyrosine Kinase/RTK >> PDGFR Signaling Pathways >> Protein Tyrosine Kinase/RTK >> FLT3 Signaling Pathways >> Protein Tyrosine Kinase/RTK >> VEGFR Signaling Pathways >> MAPK/ERK Pathway >> ERK Signaling Pathways >> Stem Cell/Wnt >> ERK
Target	VEGFR2:10 nM (Ki) VEGFR1:70 nM (Ki) MEK1:17 nM (Ki) MEK2:38 nM (Ki) FLT-3:90 nM (Ki) PDGFRα:1.5 μM (Ki) PDGFRβ:900 nM (Ki) ERK1:8.4 μM (Ki) ERK2:2.4 μM (Ki)
In Vitro	Hypothemycin inhibits eosinophilic EOL1 cell carrying mutations in FIP1L1-PDGFRα, acute myeloid leukemia MV-4-11 cell carrying mutations in FLT3-ITD, melanoma COLO829 cell carrying mutations in BRAF V600E, HUVEC cell carrying mutations in VEGFR, mastocytoma P815 cell carrying mutations in c-KIT D814Y, NSCLC A459 cell carrying mutations in KRAS, and ovarian SKOV-3 cell carrying mutations in HER2 with IC50s of 0.4 nM, 6 nM, 50 nM, 70 nM, 370 nM, 6.0 μM, and 7.0 μM, respectively[2].
In Vivo	Hypothemycin (10 mg/kg) kills T. brucei in infected mice, completely curing the infection in one third of animals, although high doses of Hypothemycin (>10 mg/kg) leads to side effects[1]. Animal Model: Adult female Balb/c mice (weighing 18–22 g) infected with T. brucei[1] Dosage: 10 mg/kg Administration: Administered once daily via intraperitoneal injection for 7 days. Result: Showed a dose-dependent reduction in parasitemia in infected mice. Prolonged survival of infected mice over 30 days, with a cure rate of 33%.
References	[1]. Schirmer A, et al. Targeted covalent inactivation of protein kinases by resorcylic acid lactone polyketides. Proc Natl Acad Sci U S A. 2006 Mar 14;103(11):4234-9. [2]. Nishino M, et al. Hypothemycin, a fungal natural product, identifies therapeutic targets in Trypanosoma brucei. Elife. 2013 Jul 9;2:e00712.

Density	1.343g/cm3
Boiling Point	673.1ºC at 760 mmHg
Melting Point	170-172℃
Molecular Formula	C₁₉H₂₂O₈
Molecular Weight	378.37300
Flash Point	242.7ºC
Exact Mass	378.13100
PSA	125.82000
LogP	1.02690
Index of Refraction	1.573
Storage condition	20°C

Hazard Codes	Xn
Risk Phrases	R22