Hypothemycin

Names

[ Name ]:
Hypothemycin

[Synonym ]:
(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

Biological Activity

[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.

Chemical & Physical Properties

[ 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

MSDS

Click to get detail MSDS

Safety Information

[ Hazard Codes ]:
Xn

[ Risk Phrases ]:
R22

Synthetic Route

Click to get detail synthetic route

Precursor & DownStream

Precursor

DownStream

Related Compounds

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