withaferin A

ID: ALA1221986

Chembl Id: CHEMBL1221986

PubChem CID: 49864510

Max Phase: Phase

Molecular Formula: C28H38O6

Molecular Weight: 470.61

Molecule Type: Small molecule

Names and Identifiers

Synonyms: Withaferin a | NSC-101088 | NSC-273757 | NSC-101088|CHEMBL1221986|DBRXOUCRJQVYJQ-BZMBVROXSA-N

Canonical SMILES:  CC1=C(CO)C(=O)O[C@H]([C@@H](C)[C@H]2CC[C@H]3[C@@H]4C[C@H]5O[C@]56[C@@H](O)C=CC(=O)[C@]6(C)[C@H]4CC[C@]23C)C1

Standard InChI:  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

Standard InChI Key:  DBRXOUCRJQVYJQ-BZMBVROXSA-N

Alternative Forms

1. Parent:

   

   ALA1221986

   WITHAFERIN A

Molecule Features

Natural Product: Yes

Oral: No

Chemical Probe: No

Parenteral: No

Molecule Type: Small molecule

Topical: No

First In Class: No

Black Box: No

Chirality: No

Availability: No

Prodrug: No

Calculated Properties

Molecular Weight: 470.61

Molecular Weight (Monoisotopic): 470.2668

AlogP: 3.35

#Rotatable Bonds: 3

Polar Surface Area: 96.36

Molecular Species: NEUTRAL

HBA: 6

HBD: 2

#RO5 Violations: ┄

HBA (Lipinski): 6

HBD (Lipinski): 2

#RO5 Violations (Lipinski): ┄

CX Acidic pKa: 13.44

CX Basic pKa: ┄

CX LogP: 3.58

CX LogD: 3.58

Aromatic Rings: ┄

Heavy Atoms: 34

QED Weighted: 0.49

Np Likeness Score: 3.88

References

1. Yokota Y, Bargagna-Mohan P, Ravindranath PP, Kim KB, Mohan R..  (2006)  Development of withaferin A analogs as probes of angiogenesis.,  16  (10): [PMID:16513346] [10.1016/j.bmcl.2006.02.039]

2. Hsieh PW, Huang ZY, Chen JH, Chang FR, Wu CC, Yang YL, Chiang MY, Yen MH, Chen SL, Yen HF, Lübken T, Hung WC, Wu YC..  (2007)  Cytotoxic withanolides from Tubocapsicum anomalum.,  70  (5): [PMID:17417907] [10.1021/np0605541]

3. Santana L, González-Díaz H, Quezada E, Uriarte E, Yáñez M, Viña D, Orallo F..  (2008)  Quantitative structure-activity relationship and complex network approach to monoamine oxidase A and B inhibitors.,  51  (21): [PMID:18834112] [10.1021/jm800656v]

4. Kaileh M, Vanden Berghe W, Heyerick A, Horion J, Piette J, Libert C, De Keukeleire D, Essawi T, Haegeman G..  (2007)  Withaferin a strongly elicits IkappaB kinase beta hyperphosphorylation concomitant with potent inhibition of its kinase activity.,  282  (7): [PMID:17150968] [10.1074/jbc.m606728200]

5. Xu YM, Marron MT, Seddon E, McLaughlin SP, Ray DT, Whitesell L, Gunatilaka AA..  (2009)  2,3-Dihydrowithaferin A-3beta-O-sulfate, a new potential prodrug of withaferin A from aeroponically grown Withania somnifera.,  17  (6): [PMID:19056281] [10.1016/j.bmc.2008.10.091]

6. Falsey RR, Marron MT, Gunaherath GM, Shirahatti N, Mahadevan D, Gunatilaka AA, Whitesell L..  (2006)  Actin microfilament aggregation induced by withaferin A is mediated by annexin II.,  2  (1): [PMID:16408090] [10.1038/nchembio755]

7. Samadi AK, Tong X, Mukerji R, Zhang H, Timmermann BN, Cohen MS..  (2010)  Withaferin A, a cytotoxic steroid from Vassobia breviflora, induces apoptosis in human head and neck squamous cell carcinoma.,  73  (9): [PMID:20726569] [10.1021/np100112p]

8. Zhang H, Samadi AK, Gallagher RJ, Araya JJ, Tong X, Day VW, Cohen MS, Kindscher K, Gollapudi R, Timmermann BN..  (2011)  Cytotoxic withanolide constituents of Physalis longifolia.,  74  (12): [PMID:22098611] [10.1021/np200635r]

9. Llanos GG, Araujo LM, Jiménez IA, Moujir LM, Bazzocchi IL..  (2012)  Withaferin A-related steroids from Withania aristata exhibit potent antiproliferative activity by inducing apoptosis in human tumor cells.,  54  [PMID:22705001] [10.1016/j.ejmech.2012.05.032]

10. Zhang H, Bazzill J, Gallagher RJ, Subramanian C, Grogan PT, Day VW, Kindscher K, Cohen MS, Timmermann BN..  (2013)  Antiproliferative withanolides from Datura wrightii.,  76  (3): [PMID:23252848] [10.1021/np300766p]

11. Roy RV, Suman S, Das TP, Luevano JE, Damodaran C..  (2013)  Withaferin A, a steroidal lactone from Withania somnifera, induces mitotic catastrophe and growth arrest in prostate cancer cells.,  76  (10): [PMID:24079846] [10.1021/np400441f]

12. Motiwala HF, Bazzill J, Samadi A, Zhang H, Timmermann BN, Cohen MS, Aubé J..  (2013)  Synthesis and Cytotoxicity of Semisynthetic Withalongolide A Analogues.,  4  (11): [PMID:24273633] [10.1021/ml400267q]

13. Wijeratne EM, Xu YM, Scherz-Shouval R, Marron MT, Rocha DD, Liu MX, Costa-Lotufo LV, Santagata S, Lindquist S, Whitesell L, Gunatilaka AA..  (2014)  Structure-activity relationships for withanolides as inducers of the cellular heat-shock response.,  57  (7): [PMID:24625088] [10.1021/jm401279n]

14. Yoneyama T, Arai MA, Sadhu SK, Ahmed F, Ishibashi M..  (2015)  Hedgehog inhibitors from Withania somnifera.,  25  (17): [PMID:26169123] [10.1016/j.bmcl.2015.06.081]

15. Xu YM, Liu MX, Grunow N, Wijeratne EM, Paine-Murrieta G, Felder S, Kris RM, Gunatilaka AA..  (2015)  Discovery of Potent 17β-Hydroxywithanolides for Castration-Resistant Prostate Cancer by High-Throughput Screening of a Natural Products Library for Androgen-Induced Gene Expression Inhibitors.,  58  (17): [PMID:26305181] [10.1021/acs.jmedchem.5b00867]

16. Cao CM, Wu X, Kindscher K, Xu L, Timmermann BN..  (2015)  Withanolides and Sucrose Esters from Physalis neomexicana.,  78  (10): [PMID:26492982] [10.1021/acs.jnatprod.5b00698]

17. Unpublished dataset, 

Source

Source(2):

• Scientific Literature
• Clinical Candidates