raltitrexed 🐶 Veterinary Use | Indications/Contra | FAERs-F | FAERs-M | Orange Bk | BioActivity |

Stem definition	Drug id	CAS RN
antineoplastics; thymidylate synthetase inhibitors	2353	112887-68-0

Description:

Molecule

Description

Molfile Inchi Smiles

Synonyms:

raltitrexed
tomudex
D-1694
ICI-D1694
ZD-1694

Molecular weight: 458.49
Formula: C21H22N4O6S
CLOGP: 1.25
LIPINSKI: 0
HAC: 10
HDO: 4
TPSA: 148.40
ALOGS: -4.40
ROTB: 9

Drug dosage:

None

ADMET properties:

Property	Value	Reference
BDDCS (Biopharmaceutical Drug Disposition Classification System)	3	Benet LZ, Broccatelli F, Oprea TI
EoM (Fraction excreted unchanged in urine)	50 %	Benet LZ, Broccatelli F, Oprea TI
BA (Bioavailability)	15 %	Kim MT, Sedykh A, Chakravarti SK, Saiakhov RD, Zhu H
Vd (Volume of distribution)	6.57 L/kg	Lombardo F, Berellini G, Obach RS
CL (Clearance)	0.90 mL/min/kg	Lombardo F, Berellini G, Obach RS
fu (Fraction unbound in plasma)	0.05 %	Lombardo F, Berellini G, Obach RS
t_half (Half-life)	140 hours	Lombardo F, Berellini G, Obach RS

Approvals:

Date	Agency	Company	Orphan
Jan. 1, 1996	YEAR INTRODUCED

FDA Adverse Event Reporting System (Female)

None

FDA Adverse Event Reporting System (Male)

MedDRA adverse event term	Likelihood ratio	Likelihood ratio threshold	Patients taking drug having adverse event	Patients taking drug not having adverse event	Patients not taking drug having adverse event	Patients not taking drug not having adverse event
Myelosuppression	91.69	45.20	27	598	19238	34937068
Bone marrow failure	68.80	45.20	24	601	29229	34927077

FDA Adverse Event Reporting System (Geriatric)

MedDRA adverse event term	Likelihood ratio	Likelihood ratio threshold	Patients taking drug having adverse event	Patients taking drug not having adverse event	Patients not taking drug having adverse event	Patients not taking drug not having adverse event
Myelosuppression	146.85	44.88	42	916	40254	79703176
Bone marrow failure	87.74	44.88	30	928	51077	79692353
Disease progression	58.86	44.88	33	925	184329	79559101
Neurotoxicity	55.38	44.88	19	939	32499	79710931
Diarrhoea	49.01	44.88	56	902	880433	78862997

FDA Adverse Event Reporting System (Pediatric)

None

Pharmacologic Action:

Source	Code	Description
ATC	L01BA03	ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS ANTINEOPLASTIC AGENTS ANTIMETABOLITES Folic acid analogues
MeSH PA	D000963	Antimetabolites
MeSH PA	D000964	Antimetabolites, Antineoplastic
MeSH PA	D000970	Antineoplastic Agents
MeSH PA	D004791	Enzyme Inhibitors
MeSH PA	D005493	Folic Acid Antagonists
MeSH PA	D009676	Noxae

Drug Use | Suggest Off label Use Form| |View source of the data|

None

🐶 Veterinary Drug Use

None

🐶 Veterinary products

None

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation level	Dissociation constant	Type (acidic/basic)
pKa1	4.16	acidic
pKa2	5.61	acidic
pKa3	9.02	acidic
pKa4	12.86	acidic
pKa5	3.53	Basic
pKa6	2.67	Basic

Orange Book patent data (new drug applications)

None

Orange Book exclusivity data (new drug applications)

None

Bioactivity Summary:

Target	Class	Pharos	UniProt	Action	Type	Activity value (-log[M])	Mechanism action	Bioact source	MoA source
Thymidylate synthase	Enzyme	P04818	TYSY_HUMAN		IC50	6.59		CHEMBL
Dihydrofolate reductase	Enzyme	P00374	DYR_HUMAN		IC50	4.68		WOMBAT-PK
Folate receptor beta	Membrane receptor	P14207	FOLR2_HUMAN		IC50	7.66		CHEMBL
Proton-coupled folate transporter	Transporter	Q96NT5	PCFT_HUMAN		IC50	7		CHEMBL
Folate transporter 1	Transporter	P41440	S19A1_HUMAN		IC50	8.20		CHEMBL
Folate receptor alpha	Membrane receptor	P15328	FOLR1_HUMAN		IC50	7.82		CHEMBL
Bifunctional dihydrofolate reductase-thymidylate synthase	Enzyme		DRTS_TOXGO		IC50	6.32		CHEMBL
Dihydrofolate reductase	Enzyme		DYR_ECOLI		IC50	4.64		CHEMBL
Thymidylate synthase	Enzyme		TYSY_ECOLI		IC50	5.24		WOMBAT-PK
Thymidylate synthase	Enzyme		TYSY_MOUSE		Ki	6.38		CHEMBL
Thymidylate synthase	Enzyme		TYSY_RAT		IC50	6.05		CHEMBL
Thymidylate synthase	Enzyme		TYSY_LACCA		IC50	5.10		CHEMBL
Dihydrofolate reductase	Enzyme		B0BL08_ECOLX		IC50	4.64		CHEMBL
Thymidylate synthase	Enzyme		C3SWJ7_ECOLX		IC50	5.28		CHEMBL

External reference:

ID	Source
D01064	KEGG_DRUG
C0677667	UMLSCUI
CHEBI:5847	CHEBI
D16	PDB_CHEM_ID
CHEMBL225071	ChEMBL_ID
DB00293	DRUGBANK_ID
C068874	MESH_SUPPLEMENTAL_RECORD_UI
7403	IUPHAR_LIGAND_ID
7319	INN_ID
FCB9EGG971	UNII
135400182	PUBCHEM_CID
196239	RXNORM
005929	NDDF
326914003	SNOMEDCT_US
395857008	SNOMEDCT_US

Pharmaceutical products:

None