Details of the Drug-Related molecule(s) Interaction Atlas

General Information of Drug (ID: DM5JKNF)

• Drug Name: Silvestrol Drug Info
• Synonyms: Naturally derived compounds (cancer); Naturally derived compounds (cancer), Bristol-Myers Squibb/National Cancer Institute

Indication

Disease Entry	ICD 11	Status	REF
Middle East Respiratory Syndrome (MERS)	1D64	Investigative	[1]
Solid tumour/cancer	2A00-2F9Z	Investigative	[2]

• Therapeutic Class: Antiviral Agents
• Cross-matching ID:
  PubChem CID: 11787114
  ChEBI ID: CHEBI:66484
  CAS Number: CAS 697235-38-4
  TTD Drug ID: DM5JKNF

Molecule-Related Drug Atlas

Drug(s) Targeting HUMAN eukaryotic initiation factor-4A (eIF4A)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
eFT226	DMHRCQI	Solid tumour/cancer	2A00-2F9Z	Phase 1/2	[4]
Hippuristanol	DM0PV2Y	T-cell leukaemia	2A90	Investigative	[5]

Drug(s) Transported By P-glycoprotein 1 (ABCB1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Amoxicillin	DMUYNEI	Acute otitis media	AB00	Approved	[6]
Doxorubicin	DMVP5YE	Acute myelogenous leukaemia	2A41	Approved	[7]
Methotrexate	DM2TEOL	Anterior urethra cancer		Approved	[8]
Folic Acid	DMEMBJC	Colorectal carcinoma		Approved	[9]
Fluorouracil	DMUM7HZ	Adenocarcinoma	2D40	Approved	[8]
Cisplatin	DMRHGI9	Adenocarcinoma	2D40	Approved	[8]
Progesterone	DMUY35B	Amenorrhea	GA20.0	Approved	[10]
Tamoxifen	DMLB0EZ	Breast cancer	2C60-2C65	Approved	[8]
Estradiol	DMUNTE3	Acne vulgaris	ED80	Approved	[11]
Imatinib	DM7RJXL	Acute lymphoblastic leukaemia	2A85	Approved	[12]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
HUMAN eukaryotic initiation factor-4A (eIF4A)	TTIGYVZ	IF4A1_HUMAN; IF4A2_HUMAN; IF4A3_HUMAN	Inhibitor	[1]

Drug Transporter (DTP)

DTP Name	DTP ID	UniProt ID	MOA	REF
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[3]

References

• [1] Broad-spectrum antiviral activity of the eIF4A inhibitor silvestrol against corona- and picornaviruses. Antiviral Res. 2018 Feb;150:123-129.
• [2] The ChEMBL database in 2017. Nucleic Acids Res. 2017 Jan 4;45(D1):D945-D954.
• [3] Resistance to the translation initiation inhibitor silvestrol is mediated by ABCB1/P-glycoprotein overexpression in acute lymphoblastic leukemia cells. AAPS J. 2011 Sep;13(3):357-64.
• [4] Design of Development Candidate eFT226, a First in Class Inhibitor of Eukaryotic Initiation Factor 4A RNA Helicase. J Med Chem. 2020 Jun 11;63(11):5879-5955.
• [5] Effects of hippuristanol, an inhibitor of eIF4A, on adult T-cell leukemia. Biochem Pharmacol. 2011 Mar 15;81(6):713-22.
• [6] Human intestinal transporter database: QSAR modeling and virtual profiling of drug uptake, efflux and interactions. Pharm Res. 2013 Apr;30(4):996-1007.
• [7] MDR1 (ABCB1) G1199A (Ser400Asn) polymorphism alters transepithelial permeability and sensitivity to anticancer agents. Cancer Chemother Pharmacol. 2009 Jun;64(1):183-8.
• [8] Mammalian drug efflux transporters of the ATP binding cassette (ABC) family in multidrug resistance: A review of the past decade. Cancer Lett. 2016 Jan 1;370(1):153-64.
• [9] Folate transporter expression decreases in the human placenta throughout pregnancy and in pre-eclampsia. Pregnancy Hypertens. 2012 Apr;2(2):123-31.
• [10] Comparative studies on in vitro methods for evaluating in vivo function of MDR1 P-glycoprotein. Pharm Res. 2001 Dec;18(12):1660-8.
• [11] Antiestrogens and steroid hormones: substrates of the human P-glycoprotein. Biochem Pharmacol. 1994 Jul 19;48(2):287-92.
• [12] Association of genetic polymorphisms in the influx transporter SLCO1B3 and the efflux transporter ABCB1 with imatinib pharmacokinetics in patients with chronic myeloid leukemia. Ther Drug Monit. 2011 Apr;33(2):244-50.