Natural Product (NP) Details

General Information of the NP (ID: NP9219)
Name
Withaferin A
Synonyms
Withaferin A; 5119-48-2; Withaferine A; NSC 273757; UNII-L6DO3QW4K5; WITHAFERIN DERIV JPR, IOWA U. COMPOUND; NSC101088; L6DO3QW4K5; NSC-101088; Ashwagandha; CHEBI:69120; 4beta,27-dihydroxy-1-oxo-5beta,6beta-epoxywitha-2,24-dienolide; (4beta,5beta,6beta,22R)-4,27-dihydroxy-5,6:22,26-diepoxyergosta-2,24-diene-1,26-dione; BRN 1335150; 5.beta.-Ergosta-2, 5,6.beta.-epoxy-4.beta.,22,27-trihydroxy-1-oxo-, .delta.-lactone, (20S,22R)-; Ergosta-2, 5,6-epoxy-4,22,27-trihydroxy-1-oxo-, .delta.-lactone, (4.beta.,5.beta.,6.beta.,22R)-; 5-19-06-00604 (Beilstein Handbook Reference); MLS006010687; SCHEMBL157208; CHEMBL517080; 5,6-Epoxy-4,27-dihydroxy-1-oxowitha-2,24-dienolide; DTXSID10965459; Withaferin A, analytical standard; Withaferin A, >=95% (HPLC); HY-N2065; ZINC8234189; MFCD10687098; NSC273757; s8587; NSC-273757; NCGC00180796-02; (4beta,5beta,6beta,22R)-5,6-Epoxy-4,22,27-trihydroxy-1-oxoergosta-2,24-dien-26-oic acid, delta-lactone; 5-beta-Ergosta-2,24-dien-26-oic acid, 5,6-beta-epoxy-4-beta,22,27-trihydroxy-1-oxo-, delta-lactone, (20S,22R)-; Ergosta-2,24-dien-26-oic acid, 5,6-epoxy-4,22,27-trihydroxy-1-oxo-, gamma-lactone, (4bta,5beta,6beta,22R)-; NCI60_000031; SMR004701668; B7199; CS-0018562; Withaferin A 100 microg/mL in Acetonitrile; C08841; A1-06845; Q6606395; BRD-K88378636-001-01-0; 4,27-Dihydroxy-5,6:22,26-diepoxyergosta-2,24-diene-1,26-dione; WLN: T3 F5 E666 1A R AXO OV PU CH&TTTTJ J1 N1 RQ IY1&- FT6OV CUTJ C1Q D1; 5beta-Ergosta-2,24-dien-26-oic acid, 5,6beta-epoxy-4beta,22,27-trihydroxy-1-oxo-, delta-lactone, (20S,22R)- (8CI); NCGC00180796-02_C28H38O6_(4beta,5beta,6beta,22R)-4,27-Dihydroxy-5,6:22,26-diepoxyergosta-2,24-diene-1,26-dione
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Species Origin Withania somnifera ...     Click to Show/Hide
Withania somnifera
Kingdom: Viridiplantae
Phylum: Streptophyta
Class: Magnoliopsida
Order: Solanales
Family: Solanaceae
Genus: Withania
Species: Withania somnifera
Disease Melanoma [ICD-11: 2C30] Terminated [1]
Structure
Click to Download Mol
2D MOL

3D MOL

ADMET Property
Absporption
Caco-2 Permeability
 -5.267
 
MDCK Permeability
 -5.003
 
PAMPA
 - - -
 
HIA
 - - -
 
Distribution
VDss
 -0.147
 
PPB
 77.8%
 
BBB
 - - -
 
Metabolism
CYP1A2 inhibitor
 - - -
CYP1A2 substrate
 - - -
CYP2C19 inhibitor
 - - -
CYP2C19 substrate
 +
CYP2C9 inhibitor
 - - -
CYP2C9 substrate
 - - -
CYP2D6 inhibitor
 - - -
CYP2D6 substrate
 - - -
CYP3A4 inhibitor
 - - -
CYP3A4 substrate
 - -
CYP2B6 inhibitor
 +++
CYP2B6 substrate
 - - -
CYP2C8 inhibitor
 +++
HLM Stability
 +++
 
Excretion
CLplasma
 9.079
 
T1/2
 1.405
Toxicity
DILI
 - -
 
Rat Oral Acute Toxicity
 - -
 
FDAMDD
 +
 
Respiratory
 ++
 
Human Hepatotoxicity
 -
 
Ototoxicity
 +
 
Drug-induced Nephrotoxicity
 +
 
Drug-induced Neurotoxicity
 - - -
 
Hematotoxicity
 -
 
Genotoxicity
 +
 
Tips: 1. For the classification endpoints, the prediction probability values are transformed into six symbols: 0-0.1 (- - -), 0.1-0.3 (- -), 0.3-0.5 (-), 0.5-0.7 (+), 0.7-0.9 (++), and 0.9-1.0 (+++). 2. Additionally, the corresponding relationships of the three labels are as follows: excellent; medium; poor.
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    Click to Show/Hide the Molecular Information and External Link(s) of This Natural Product
Formula
C28H38O6
PubChem CID
265237
Canonical SMILES
CC1=C(C(=O)OC(C1)C(C)C2CCC3C2(CCC4C3CC5C6(C4(C(=O)C=CC6O)C)O5)C)CO
InChI
1S/C28H38O6/c1-14-11-21(33-25(32)17(14)13-29)15(2)18-5-6-19-16-12-24-28(34-24)23(31)8-7-22(30)27(28,4)20(16)9-10-26(18,19)3/h7-8,15-16,18-21,23-24,29,31H,5-6,9-13H2,1-4H3/t15-,16-,18+,19-,20-,21+,23-,24+,26+,27-,28+/m0/s1
InChIKey
DBRXOUCRJQVYJQ-CKNDUULBSA-N
CAS Number
CAS 5119-48-2
ChEBI ID
CHEBI:69120
Herb ID
HBIN048300
SymMap ID
SMIT18226
TTD Drug ID
D0V3PN
Combinatorial Therapeutic Effect(s) Validated Clinically or Experimentally
    α. A List of Drug(s) Whose Efficacy can be Enhanced by This NP
          Caffeic acid phenethyl ester      Ovarian cancer     Click to Show/Hide the Molecular Data of This Drug
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [2]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Down-regulation Expression TP53  Molecule Info 
Pathway MAP
                    In-vitro Model SK-OV-3 CVCL_0532 Ovarian serous cystadenocarcinoma Homo sapiens
OVK18 CVCL_3770 Ovarian endometrioid adenocarcinoma Homo sapiens
HeLa CVCL_0030 Endocervical adenocarcinoma Homo sapiens
SKG-II CVCL_2794 Cervical squamous cell carcinoma Homo sapiens
SKG-IIIb CVCL_2795 Cervical squamous cell carcinoma Homo sapiens
ME-180 CVCL_1401 Cervical squamous cell carcinoma Homo sapiens
                    In-vivo Model Effect of Wi-A, CAPE and their combination was examined by female 4-5 weeks old BALB/c nude mice in vivo tumor growth assay using subcutaneous xenografts of SKOV-3.
                    Experimental
                    Result(s)		 A combination of Wi-A and CAPE offers selective toxicity and better potency to cancer cells.
          Sorafenib      Renal cell carcinoma     Click to Show/Hide the Molecular Data of This Drug
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [3]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Down-regulation Phosphorylation CASP3  Molecule Info 
Pathway MAP
Down-regulation Expression PARP1  Molecule Info 
Pathway MAP
                    In-vitro Model B-CPAP CVCL_0153 Thyroid gland carcinoma Homo sapiens
SW1736 CVCL_3883 Thyroid gland anaplastic carcinoma Homo sapiens
                    Experimental
                    Result(s)		 Combination therapy with sorafenib + withaferin showed synergistic efficacy in papillary and anaplastic cancers in vitro with significant induction of apoptosis.
Target and Pathway
Target(s) Apoptosis regulator Bcl-2 (BCL-2)  Molecule Info 
PI3-kinase alpha  Molecule Info 
Protein kinase B alpha (AKT1)  Molecule Info 
STAT factor 3 (STAT3)  Molecule Info 
References
Reference 1 Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800006527)
Reference 2 Combination of Withaferin-A and CAPE Provides Superior Anticancer Potency: Bioinformatics and Experimental Evidence to Their Molecular Targets and Mechanism of Action. Cancers (Basel). 2020 May 5;12(5):1160.
Reference 3 A novel combination of withaferin A and sorafenib shows synergistic efficacy against both papillary and anaplastic thyroid cancers. Am J Surg. 2012 Dec;204(6):895-900; discussion 900-1.
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