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

Stem definition	Drug id	CAS RN
folic acid analogues	4117	146464-95-1

Description:

Molecule	Description
Molfile Inchi Smiles Synonyms: 10-Propargyl-10-deazaaminopterin pralatrexate folotyn	Pralatrexate is a folate analog metabolic inhibitor that competitively inhibits dihydrofolate reductase. It is also a competitive inhibitor for polyglutamylation by the enzyme folylpolyglutamyl synthetase. This inhibition results in the depletion of thymidine and other biological molecules the synthesis of which depends on single carbon transfer. Molecular weight: 477.48 Formula: C23H23N7O5 CLOGP: 0.39 LIPINSKI: 1 HAC: 12 HDO: 5 TPSA: 207.30 ALOGS: -4.43 ROTB: 10 Status: OFP Legend: OFP - off patent OFM - off market ONP - on patent

Molecule

Description

Molfile Inchi Smiles

Synonyms:

10-Propargyl-10-deazaaminopterin
pralatrexate
folotyn

Pralatrexate is a folate analog metabolic inhibitor that competitively inhibits dihydrofolate reductase. It is also a competitive inhibitor for polyglutamylation by the enzyme folylpolyglutamyl synthetase. This inhibition results in the depletion of thymidine and other biological molecules the synthesis of which depends on single carbon transfer.

Molecular weight: 477.48
Formula: C23H23N7O5
CLOGP: 0.39
LIPINSKI: 1
HAC: 12
HDO: 5
TPSA: 207.30
ALOGS: -4.43
ROTB: 10

Status: OFP

Legend:
OFP - off patent
OFM - off market
ONP - on patent

Drug dosage:

None

ADMET properties:

Property	Value	Reference
Vd (Volume of distribution)	0.53 L/kg	Lombardo F, Berellini G, Obach RS
CL (Clearance)	2.70 mL/min/kg	Lombardo F, Berellini G, Obach RS
fu (Fraction unbound in plasma)	0.33 %	Lombardo F, Berellini G, Obach RS
t_half (Half-life)	15 hours	Lombardo F, Berellini G, Obach RS

Approvals:

Date	Agency	Company	Orphan
Sept. 24, 2009	FDA	ALLOS
July 3, 2017	PMDA	Mundipharma KK

FDA Adverse Event Reporting System (Female)

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
Malignant neoplasm progression	108.00	58.08	35	445	82086	63406456
Stomatitis	72.55	58.08	30	450	138695	63349847

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
Stomatitis	188.02	50.58	57	617	42457	34913800
Malignant neoplasm progression	126.08	50.58	51	623	87995	34868262
Mucosal inflammation	74.86	50.58	28	646	38594	34917663
Platelet count decreased	66.06	50.58	36	638	119681	34836576
Disease progression	52.68	50.58	30	644	108047	34848210
Neutrophil count decreased	50.81	50.58	23	651	51081	34905176

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
Stomatitis	218.69	51.27	81	1075	146676	79596556
Malignant neoplasm progression	209.68	51.27	77	1079	135913	79607319
Platelet count decreased	109.36	51.27	54	1102	194610	79548622
Mucosal inflammation	98.45	51.27	38	1118	75542	79667690
Neutrophil count decreased	73.99	51.27	33	1123	93926	79649306
Disease progression	55.58	51.27	34	1122	184328	79558904

FDA Adverse Event Reporting System (Pediatric)

None

Pharmacologic Action:

Source	Code	Description
ATC	L01BA05	ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS ANTINEOPLASTIC AGENTS ANTIMETABOLITES Folic acid analogues
FDA EPC	N0000175584	Folate Analog Metabolic Inhibitor
CHEBI has role	CHEBI:35221	antimetabolite
CHEBI has role	CHEBI:35610	antineoplastic agents
CHEBI has role	CHEBI:50683	dihydrofolic acid reductase inhibitors

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

Disease	Relation	SNOMED_ID	DOID
Peripheral T-cell lymphoma	indication	109977009
Stomatitis	contraindication	61170000	DOID:9637
Liver function tests abnormal	contraindication	166603001
Impaired renal function disorder	contraindication	197663003
Anemia	contraindication	271737000	DOID:2355
Pregnancy, function	contraindication	289908002
Thrombocytopenic disorder	contraindication	302215000	DOID:1588
Neutropenic disorder	contraindication	303011007	DOID:1227
Bone marrow depression	contraindication	307762000
Breastfeeding (mother)	contraindication	413712001

🐶 Veterinary Drug Use

None

🐶 Veterinary products

None

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation level	Dissociation constant	Type (acidic/basic)
pKa1	3.61	acidic
pKa2	5.29	acidic
pKa3	13.13	acidic
pKa4	4.6	Basic
pKa5	4.51	Basic
pKa6	1.39	Basic
pKa7	0.14	Basic

Orange Book patent data (new drug applications)

Formulation strength	Trade name	Applicant	Application number	Approval date	Type	Dose form	Route	Patent number	Patent expiration date	Patent use
20MG/ML (20MG/ML)	FOLOTYN	ACROTECH BIOPHARMA	N022468	Sept. 24, 2009	RX	SOLUTION	INTRAVENOUS	7622470	May 31, 2025	TREATMENT OF PATIENTS WITH RELAPSED OR REFRACTORY PERIPHERAL T-CELL LYMPHOMA
20MG/ML (20MG/ML)	FOLOTYN	ACROTECH BIOPHARMA	N022468	Sept. 24, 2009	RX	SOLUTION	INTRAVENOUS	8299078	May 31, 2025	TREATMENT OF PATIENTS WITH RELAPSED OR REFRACTORY PERIPHERAL T-CELL LYMPHOMA
40MG/2ML (20MG/ML)	FOLOTYN	ACROTECH BIOPHARMA	N022468	Sept. 24, 2009	RX	SOLUTION	INTRAVENOUS	7622470	May 31, 2025	TREATMENT OF PATIENTS WITH RELAPSED OR REFRACTORY PERIPHERAL T-CELL LYMPHOMA
40MG/2ML (20MG/ML)	FOLOTYN	ACROTECH BIOPHARMA	N022468	Sept. 24, 2009	RX	SOLUTION	INTRAVENOUS	8299078	May 31, 2025	TREATMENT OF PATIENTS WITH RELAPSED OR REFRACTORY PERIPHERAL T-CELL LYMPHOMA

Orange Book exclusivity data (new drug applications)

None

Bioactivity Summary:

Target	Class	Pharos	UniProt	Action	Type	Activity value (-log[M])	Bioact source	MoA source
Dihydrofolate reductase	Enzyme	P00374	DYR_HUMAN	INHIBITOR	Ki	7.35	IUPHAR	CHEMBL
Proton-coupled folate transporter	Transporter	Q96NT5	PCFT_HUMAN		IC50	7.24	CHEMBL
Folate transporter 1	Transporter	P41440	S19A1_HUMAN		IC50	9.16	CHEMBL
Folate receptor alpha	Membrane receptor	P15328	FOLR1_HUMAN		IC50	6.78	CHEMBL

External reference:

ID	Source
4029347	VUID
N0000180303	NUI
D05589	KEGG_DRUG
4029347	VANDF
C1721300	UMLSCUI
CHEBI:71223	CHEBI
CHEMBL1201746	ChEMBL_ID
DB06813	DRUGBANK_ID
C418863	MESH_SUPPLEMENTAL_RECORD_UI
6840	IUPHAR_LIGAND_ID
8560	INN_ID
A8Q8I19Q20	UNII
148121	PUBCHEM_CID
662019	RXNORM
168008	MMSL
26748	MMSL
364303	MMSL
d07492	MMSL
013258	NDDF
428598004	SNOMEDCT_US
429320009	SNOMEDCT_US
895675003	SNOMEDCT_US

Pharmaceutical products:

Product	Category	Ingredients	NDC	Form	Quantity	Route	Marketing	Label
Folotyn	Human Prescription Drug Label	1	48818-001	INJECTION	20 mg	INTRAVENOUS	NDA	27 sections
Folotyn	Human Prescription Drug Label	1	48818-001	INJECTION	20 mg	INTRAVENOUS	NDA	27 sections
Pralatrexate	HUMAN PRESCRIPTION DRUG LABEL	1	65219-550	INJECTION	20 mg	INTRAVENOUS	NDA authorized generic	29 sections
Pralatrexate	HUMAN PRESCRIPTION DRUG LABEL	1	65219-552	INJECTION	40 mg	INTRAVENOUS	NDA authorized generic	29 sections
Folotyn	Human Prescription Drug Label	1	72893-003	INJECTION	20 mg	INTRAVENOUS	NDA	29 sections
Folotyn	Human Prescription Drug Label	1	72893-003	INJECTION	20 mg	INTRAVENOUS	NDA	29 sections
Folotyn	Human Prescription Drug Label	1	72893-003	INJECTION	20 mg	INTRAVENOUS	NDA	29 sections
Folotyn	Human Prescription Drug Label	1	72893-005	INJECTION	40 mg	INTRAVENOUS	NDA	29 sections
Folotyn	Human Prescription Drug Label	1	72893-005	INJECTION	40 mg	INTRAVENOUS	NDA	29 sections
Folotyn	Human Prescription Drug Label	1	72893-005	INJECTION	40 mg	INTRAVENOUS	NDA	29 sections