Details of the Drug

General Information of Drug (ID: DMT9K8G)

Drug Name

Raltitrexed

Synonyms

Tomudex; 112887-68-0; ZD1694; ZD-1694; ICI-D1694; D-1694; ZD 1694; ICI D1694; UNII-FCB9EGG971; D1694; D 1694; CHEBI:5847; Raltitrexed (Tomudex); C21H22N4O6S; ZD-16; (2S)-2-[[5-[methyl-[(2-methyl-4-oxo-1H-quinazolin-6-yl)methyl]amino]thiophene-2-carbonyl]amino]pentanedioic acid; FCB9EGG971; CHEMBL225071; N-(5-(N-(3,4-Dihydro-2-methyl-4-oxoquinazolin-6-ylmethyl)-N-methylamino)-2-thenoyl)-L-glutamic acid; ICI-D-1694; NSC-639186; NCGC00229704-01; DSSTox_RID_81653; DSSTox_CID_26482; DSSTox_GSID_46482

Indication

Disease Entry	ICD 11	Status	REF
Rectal adenocarcinoma	2B92	Approved	[1]
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Therapeutic Class

Anticancer Agents

Drug Type

Small molecular drug

Structure

3D MOL

2D MOL

#Ro5 Violations (Lipinski): 0

Molecular Weight (mw)

458.5

Logarithm of the Partition Coefficient (xlogp)

1.4

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 3: high solubility and low permeability [2]
Clearance: The drug present in the plasma can be removed from the body at the rate of 0.9 mL/min/kg [3]
Elimination: 50% 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 198 hours [3]
Metabolism: The drug is metabolized via a reduced folate carrier []
Unbound Fraction: The unbound fraction of drug in plasma is 0.05% [3]
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 6.57 L/kg [3]

Chemical Identifiers

Formula: C21H22N4O6S
IUPAC Name: (2S)-2-[[5-[methyl-[(2-methyl-4-oxo-3H-quinazolin-6-yl)methyl]amino]thiophene-2-carbonyl]amino]pentanedioic acid
Canonical SMILES: CC1=NC2=C(C=C(C=C2)CN(C)C3=CC=C(S3)C(=O)N[C@@H](CCC(=O)O)C(=O)O)C(=O)N1
InChI: InChI=1S/C21H22N4O6S/c1-11-22-14-4-3-12(9-13(14)19(28)23-11)10-25(2)17-7-6-16(32-17)20(29)24-15(21(30)31)5-8-18(26)27/h3-4,6-7,9,15H,5,8,10H2,1-2H3,(H,24,29)(H,26,27)(H,30,31)(H,22,23,28)/t15-/m0/s1
InChIKey: IVTVGDXNLFLDRM-HNNXBMFYSA-N

Cross-matching ID

PubChem CID: 135400182
ChEBI ID: CHEBI:5847
CAS Number: 112887-68-0
DrugBank ID: DB00293
TTD ID: D01KKQ
VARIDT ID: DR00958

Combinatorial Drugs (CBD)

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Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Candida Thymidylate synthase (Candi TMP1)	TTU6BFZ	TYSY_CANAL	Inhibitor	[4]

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Drug Transporter (DTP)

DTP Name	DTP ID	UniProt ID	MOA	REF
Multidrug resistance-associated protein 2 (ABCC2)	DTFI42L	MRP2_HUMAN	Substrate	[5]
Breast cancer resistance protein (ABCG2)	DTI7UX6	ABCG2_HUMAN	Substrate	[6]

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Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
10 kDa heat shock protein, mitochondrial (HSPE1)	OT7JSZLB	CH10_HUMAN	Gene/Protein Processing	[7]
Annexin A2 (ANXA2)	OTFNS0CC	ANXA2_HUMAN	Gene/Protein Processing	[7]
Cellular tumor antigen p53 (TP53)	OTIE1VH3	P53_HUMAN	Drug Response	[8]
Diamine acetyltransferase 1 (SAT1)	OT52AU22	SAT1_HUMAN	Gene/Protein Processing	[7]
Folate receptor alpha (FOLR1)	OT0QZ0H6	FOLR1_HUMAN	Drug Response	[9]
FXYD domain-containing ion transport regulator 3 (FXYD3)	OT9PPRHE	FXYD3_HUMAN	Gene/Protein Processing	[7]
Proton-coupled folate transporter (SLC46A1)	OT049V7Y	PCFT_HUMAN	Drug Response	[9]
Reduced folate transporter (SLC19A1)	OTWB0BTO	S19A1_HUMAN	Drug Response	[10]
Signal transducer and activator of transcription 1-alpha/beta (STAT1)	OTLMBUZ6	STAT1_HUMAN	Post-Translational Modifications	[11]
Thymidylate synthase	OTXTG0C7	TYSY_HUMAN	Gene/Protein Processing	[8]

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Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This Drug

References

1	URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7403).
2	BDDCS applied to over 900 drugs
3	Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
4	DNA damage and homologous recombination signaling induced by thymidylate deprivation. Biochem Pharmacol. 2008 Oct 15;76(8):987-96.
5	Antifolate resistance mediated by the multidrug resistance proteins MRP1 and MRP2. Cancer Res. 1999 Jun 1;59(11):2532-5.
6	Pharmacogenomic importance of ABCG2. Pharmacogenomics. 2008 Aug;9(8):1005-9.
7	5-Fluorouracil: identification of novel downstream mediators of tumour response. Anticancer Res. 2004 Mar-Apr;24(2A):417-23.
8	Changes in the status of p53 affect drug sensitivity to thymidylate synthase (TS) inhibitors by altering TS levels. Br J Cancer. 2007 Mar 12;96(5):769-75.
9	Synthesis, biological, and antitumor activity of a highly potent 6-substituted pyrrolo[2,3-d]pyrimidine thienoyl antifolate inhibitor with proton-coupled folate transporter and folate receptor selectivity over the reduced folate carrier that inhibits -glycinamide ribonucleotide formyltransferase. J Med Chem. 2011 Oct 27;54(20):7150-64.
10	The inverse relationship between reduced folate carrier function and pemetrexed activity in a human colon cancer cell line. Mol Cancer Ther. 2006 Feb;5(2):438-49. doi: 10.1158/1535-7163.MCT-05-0243.
11	Effect of p53 status and STAT1 on chemotherapy-induced, Fas-mediated apoptosis in colorectal cancer. Cancer Res. 2005 Oct 1;65(19):8951-60. doi: 10.1158/0008-5472.CAN-05-0961.