Details of the Drug

General Information of Drug (ID: DM5FL14)

Drug Name

Amifostine

Synonyms

Ethiofos; Ethyol; Gammaphos; WR-1064; WR-2721; WR-2721C; YM-08310

Indication

Disease Entry	ICD 11	Status	REF
Mucositis	CA00	Approved	[1]
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Drug Type

Small molecular drug

Structure

3D MOL

2D MOL

#Ro5 Violations (Lipinski): 1

Molecular Weight (mw)

214.23

Logarithm of the Partition Coefficient (xlogp)

-4.5

Rotatable Bond Count (rotbonds)

Hydrogen Bond Donor Count (hbonddonor)

Hydrogen Bond Acceptor Count (hbondacc)

ADMET Property

BDDCS Class: Biopharmaceutics Drug Disposition Classification System (BDDCS) Class 1: high solubility and high permeability [2]
Bioavailability: 99% of drug becomes completely available to its intended biological destination(s) [3]
Clearance: The drug present in the plasma can be removed from the body at the rate of 30.65 mL/min/kg [4]
Elimination: 0.69% of drug is excreted from urine in the unchanged form [2]
Half-life: The concentration or amount of drug in body reduced by one-half in 8 minutes [4]
Metabolism: The drug is metabolized via the alkaline phosphatase in tissues primarily to the active free thiol metabolite and, subsequently, to a less active disulfide metabolite []
MRTD: The Maximum Recommended Therapeutic Dose (MRTD) of drug that ensured maximising efficacy and moderate side effect is 105 micromolar/kg/day [5]
Vd: Fluid volume that would be required to contain the amount of drug present in the body at the same concentration as in the plasma 0.09 L/kg [4]

Chemical Identifiers

Formula: C5H15N2O3PS
IUPAC Name: 2-(3-aminopropylamino)ethylsulfanylphosphonic acid
Canonical SMILES: C(CN)CNCCSP(=O)(O)O
InChI: InChI=1S/C5H15N2O3PS/c6-2-1-3-7-4-5-12-11(8,9)10/h7H,1-6H2,(H2,8,9,10)
InChIKey: JKOQGQFVAUAYPM-UHFFFAOYSA-N

Cross-matching ID

Combinatorial Drugs (CBD)

Repurposed Drugs (RPD)

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Toxic reactive metabolite (TRM)	TT0C9DV	NOUNIPROTAC	Modulator	[1]

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Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Alkaline phosphatase (ALPL)_{Main DME}	DEVEFKM	PPBT_HUMAN	Substrate	[6]

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Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Cellular tumor antigen p53 (TP53)	OTIE1VH3	P53_HUMAN	Gene/Protein Processing	[7]
Cyclin-dependent kinase 1 (CDK1)	OTW1SC2N	CDK1_HUMAN	Post-Translational Modifications	[7]
Cyclin-dependent kinase inhibitor 1 (CDKN1A)	OTQWHCZE	CDN1A_HUMAN	Gene/Protein Processing	[8]
E3 ubiquitin-protein ligase Mdm2 (MDM2)	OTOVXARF	MDM2_HUMAN	Gene/Protein Processing	[8]
Etoposide-induced protein 2.4 homolog (EI24)	OTD4NOYS	EI24_HUMAN	Gene/Protein Processing	[8]
Quinone oxidoreductase PIG3 (TP53I3)	OTSCM68G	QORX_HUMAN	Gene/Protein Processing	[8]
Transcription factor p65 (RELA)	OTUJP9CN	TF65_HUMAN	Protein Interaction/Cellular Processes	[9]

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Molecular Interaction Atlas (MIA)

Jump to Detail Molecular Interaction Atlas of This Drug

Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Disease Different from Amifostine (Comorbidity)

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Comorbidity	REF
Etelcalcetide	DMHP9BL	Major	Increased risk of hypocalcemia by the combination of Amifostine and Etelcalcetide.	Hyper-parathyroidism [5A51]	[10]
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References

1	Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
2	BDDCS applied to over 900 drugs
3	Critical Evaluation of Human Oral Bioavailability for Pharmaceutical Drugs by Using Various Cheminformatics Approaches
4	Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
5	Estimating the safe starting dose in phase I clinical trials and no observed effect level based on QSAR modeling of the human maximum recommended daily dose
6	Pharmacokinetic profile of amifostine. Semin Oncol. 1996 Aug;23(4 Suppl 8):18-22.
7	Induction of apoptosis in human lung cancer cells following treatment with amifostine and an adenoviral vector containing wild-type p53. Cancer Gene Ther. 2006 Aug;13(8):806-14. doi: 10.1038/sj.cgt.7700960. Epub 2006 Apr 21.
8	Amifostine impairs p53-mediated apoptosis of human myeloid leukemia cells. Mol Cancer Ther. 2003 Sep;2(9):893-900.
9	Amifostine inhibits hematopoietic progenitor cell apoptosis by activating NF-kappaB/Rel transcription factors. Blood. 1999 Dec 15;94(12):4060-6.
10	Cerner Multum, Inc. "UK Summary of Product Characteristics.".