WITHAFERIN A

ID: ALA1221986

Max Phase: Phase

Molecular Formula: C28H38O6

Molecular Weight: 470.61

Molecule Type: Small molecule

Associated Items:

Representations

Synonyms (3): Withaferin a | NSC-101088 | NSC-273757
Synonyms from Alternative Forms(3):

    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

    Associated Targets(Human)

    HUVEC 11049 Activities

    Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

    HepG2 196354 Activities

    Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

    MCF7 126967 Activities

    Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

    A549 127892 Activities

    Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

    MDA-MB-231 73002 Activities

    Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

    MRC5 9203 Activities

    Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

    WI-38 2654 Activities

    Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

    Serine/threonine-protein kinase AKT 9192 Activities

    Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

    Mitogen-activated protein kinase; ERK1/ERK2 651 Activities

    Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

    Heat shock cognate 71 kDa protein 193 Activities

    Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

    Annexin A2 15 Activities

    Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

    SK-MEL-28 48833 Activities

    Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

    HeLa 62764 Activities

    Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

    Caspase-3 3632 Activities

    Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

    U-251 51189 Activities

    Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

    DU-145 51482 Activities

    Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

    PC-3 62116 Activities

    Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

    Tubulin alpha 84 Activities

    Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

    Serine/threonine-protein kinase Aurora-B 6805 Activities

    Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

    Cyclin-dependent kinase 1/cyclin B1 1887 Activities

    Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

    Serine/threonine-protein kinase Chk1 6846 Activities

    Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

    Serine/threonine-protein kinase Chk2 4015 Activities

    Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

    Cyclin-dependent kinase 1 3927 Activities

    Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

    Dual specificity phosphatase Cdc25C 295 Activities

    Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

    Serine/threonine-protein kinase WEE1 1772 Activities

    Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

    Heat shock 70 kDa protein 6 44 Activities

    Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

    LNCaP 8286 Activities

    Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

    NCI-H460 60772 Activities

    Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

    SF-268 49410 Activities

    Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

    HFF 3142 Activities

    Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

    HaCaT 4069 Activities

    Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

    PANC-1 6144 Activities

    Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

    Zinc finger protein GLI1 201 Activities

    Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

    Associated Targets(non-human)

    Inhibitor of nuclear factor kappa-B kinase subunit beta 81 Activities

    Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

    Mus musculus 284745 Activities

    Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

    Monoamine oxidase A 498 Activities

    Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

    Monoamine oxidase B 346 Activities

    Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

    Heat shock factor protein 1 5445 Activities

    Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

    Annexin A6 1 Activities

    Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

    Annexin A4 1 Activities

    Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

    Annexin A2 5 Activities

    Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

    Annexin A1 1 Activities

    Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

    Annexin A5 1 Activities

    Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

    B16-F10 4610 Activities

    Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

    Vero 26788 Activities

    Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

    Molecule Features

    Natural Product: YesOral: NoChemical Probe: NoParenteral: No
    Molecule Type: Small moleculeTopical: NoFirst In Class: NoBlack Box: No
    Chirality: NoAvailability: NoProdrug: No

    Drug Indications

    MESH IDMESH Heading EFO IDsEFO TermsMax Phase for IndicationReferences

    Mechanisms of Action

    Mechanism of ActionAction Typetarget IDTarget NameTarget TypeTarget OrganismBinding Site NameReferences

    Properties

    Molecular Weight: 470.61Molecular Weight (Monoisotopic): 470.2668AlogP: 3.35#Rotatable Bonds: 3
    Polar Surface Area: 96.36Molecular Species: NEUTRALHBA: 6HBD: 2
    #RO5 Violations: 0HBA (Lipinski): 6HBD (Lipinski): 2#RO5 Violations (Lipinski): 0
    CX Acidic pKa: 13.44CX Basic pKa: CX LogP: 3.58CX LogD: 3.58
    Aromatic Rings: 0Heavy Atoms: 34QED Weighted: 0.49Np 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.,  (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.,  (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,