ZAVEGEPANT

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C36H46N8O3
Molecular Weight	638.8022
Optical Activity	UNSPECIFIED
Defined Stereocenters	1 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CN1CCC(CC1)N2CCN(CC2)C(=O)[C@@H](CC3=CC4=C(NN=C4)C(C)=C3)NC(=O)N5CCC(CC5)C6=CC7=C(NC6=O)C=CC=C7

InChI

InChIKey=JJVAPHYEOZSKJZ-JGCGQSQUSA-N

InChI=1S/C36H46N8O3/c1-24-19-25(20-28-23-37-40-33(24)28)21-32(35(46)43-17-15-42(16-18-43)29-9-11-41(2)12-10-29)39-36(47)44-13-7-26(8-14-44)30-22-27-5-3-4-6-31(27)38-34(30)45/h3-6,19-20,22-23,26,29,32H,7-18,21H2,1-2H3,(H,37,40)(H,38,45)(H,39,47)/t32-/m1/s1

HIDE SMILES / InChI

Description
Sources: https://pubmed.ncbi.nlm.nih.gov/37227596|https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/216386s000lbl.pdf

Zavegepant is a third generation, small-molecule, calcitonin gene-related peptide (CGRP) receptor antagonist being developed by Pfizer, under a license from Bristol-Myers Squibb, for the prevention and treatment of chronic and episodic migraine. In March 2023, zavegepant nasal spray (ZAVZPRET™) received its first approval in the USA for the acute treatment of migraine with or without aura in adults, based on two randomized, double-blind, placebo-controlled studies. Clinical development of an oral formulation of zavegepant is currently underway.

CNS Activity

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Calcitonin gene-related peptide type 1 receptor 9 Target ID: CHEMBL3798 Gene ID: 10203.0 Target Organism: Homo sapiens (Human) Sources: https://pubmed.ncbi.nlm.nih.gov/33096162/	Antagonist 2849		0.023 nM [Ki]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Migraine 107 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/216386s000lbl.pdf	Primary		Approved 8583	ZAVZPRET Approved Use ZAVZPRET is a calcitonin gene-related peptide receptor antagonist indicated for the acute treatment of migraine with or without aura in adults. Launch Date 2023

T_1/2

Value	Dose	Co-administered	Analyte	Population
6.55 h DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/216386s000lbl.pdf	10 mg single, nasal dose: 10 mg route of administration: Nasal experiment type: SINGLE co-administered:		ZAVEGEPANT plasma	Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN

F_unbound

Value	Dose	Co-administered	Analyte	Population
10% DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/216386s000lbl.pdf	10 mg single, nasal dose: 10 mg route of administration: Nasal experiment type: SINGLE co-administered:		ZAVEGEPANT plasma	Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1946 inhibitor 2252 inducer 1087	inhibitor 2438	substrate 1388 inhibitor 2507	inhibitor 2217

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
OATP1B1 1079 OAT1 725 MATE2-K 77 OAT3 747 OCT2 779 OATP1B3 961 MATE1 415 OAT2 153 OATP2B1 157 CYP1A2 2153 CYP2C19 2057 CYP2B6 926 CYP2C8 1057 P-gp 1741 BCRP 910	MRP3 58 OATP1B1 503 P-gp 2052 OAT1 395 BSEP 63 OATP1B3 435 MATE1 182 OAT3 391 NTCP 22 BCRP 697 MRP4 91 OCT2 434 MRP2 252 MATE2-K 33	CYP3A5 92 CYP2B6 669 CYP1A2 832

Drug as perpetrator

Target	Modality	Activity
BCRP 985	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2023/216386Orig1s000ClinPharmR.pdf Page: 15 \| 28	no [IC50 >100 uM]
OAT1 730	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2023/216386Orig1s000ClinPharmR.pdf Page: 15 \| 28	no [IC50 >100 uM]
OAT3 749	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2023/216386Orig1s000ClinPharmR.pdf Page: 15 \| 28	no [IC50 >100 uM]
P-gp 1932	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2023/216386Orig1s000ClinPharmR.pdf Page: 15 \| 28	no [IC50 >100 uM]
CYP1A2 2333	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2023/216386Orig1s000ClinPharmR.pdf Page: 15.0	no
CYP1A2 2333	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2023/216386Orig1s000ClinPharmR.pdf Page: 15.0	no
CYP2B6 1160	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2023/216386Orig1s000ClinPharmR.pdf Page: 15.0	no
CYP2B6 1160	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2023/216386Orig1s000ClinPharmR.pdf Page: 15.0	no
CYP2C19 2141	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2023/216386Orig1s000ClinPharmR.pdf Page: 15.0	no
CYP2C8 1117	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2023/216386Orig1s000ClinPharmR.pdf Page: 15.0	no
CYP2C9 2497	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2023/216386Orig1s000ClinPharmR.pdf Page: 15.0	no
CYP2D6 2546	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2023/216386Orig1s000ClinPharmR.pdf Page: 15.0	no
CYP3A4 2633	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2023/216386Orig1s000ClinPharmR.pdf Page: 15.0	no
CYP3A5 201	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2023/216386Orig1s000ClinPharmR.pdf Page: 15.0	no
OATP1B1 1095	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2023/216386Orig1s000PharmR.pdf Page: 13 \| 17	weak [IC50 >40 uM]
OATP1B3 970	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2023/216386Orig1s000PharmR.pdf Page: 13 \| 17	weak [IC50 >40 uM]
CYP3A4 2633	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2023/216386Orig1s000PharmR.pdf Page: 17.0	weak [IC50 >50 uM]
MATE1 416	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2023/216386Orig1s000PharmR.pdf Page: 16.0	yes [IC50 0.158 uM]
OCT2 782	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2023/216386Orig1s000PharmR.pdf Page: 16.0	yes [IC50 2.15 uM]
MATE2-K 77	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2023/216386Orig1s000PharmR.pdf Page: 16.0	yes [IC50 4.96 uM]
OAT2 155	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2023/216386Orig1s000PharmR.pdf Page: 13.0	yes
OATP2B1 162	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2023/216386Orig1s000PharmR.pdf Page: 13.0	yes

Drug as victim

Target	Modality	Activity	Clinical evidence
CYP2D6 1388	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2023/216386Orig1s000PharmR.pdf Page: 17.0	major
CYP3A4 1946	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2023/216386Orig1s000PharmR.pdf \| https://www.accessdata.fda.gov/drugsatfda_docs/nda/2023/216386Orig1s000ClinPharmR.pdf#page=10 Page: 17.0	major	no (co-administration study) Comment: Itraconazole did not result in a clinically relevant effect on the exposures of zavegepant. Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2023/216386Orig1s000PharmR.pdf \| https://www.accessdata.fda.gov/drugsatfda_docs/nda/2023/216386Orig1s000ClinPharmR.pdf#page=10 Page: 17.0
BCRP 697	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2023/216386Orig1s000ClinPharmR.pdf Page: 15.0	no
BSEP 63	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2023/216386Orig1s000ClinPharmR.pdf Page: 15.0	no
MRP2 252	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2023/216386Orig1s000ClinPharmR.pdf Page: 15.0	no
MRP3 58	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2023/216386Orig1s000ClinPharmR.pdf Page: 15.0	no
MRP4 91	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2023/216386Orig1s000ClinPharmR.pdf Page: 15.0	no
OAT1 395	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2023/216386Orig1s000ClinPharmR.pdf Page: 15.0	no
OAT3 391	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2023/216386Orig1s000ClinPharmR.pdf Page: 15.0	no
OATP1B1 503	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2023/216386Orig1s000ClinPharmR.pdf Page: 15.0	no
OCT2 434	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2023/216386Orig1s000ClinPharmR.pdf Page: 15.0	no
MATE1 182	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2023/216386Orig1s000PharmR.pdf Page: 16.0	yes
MATE2-K 33	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2023/216386Orig1s000PharmR.pdf Page: 16.0	yes
P-gp 2052	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2023/216386Orig1s000PharmR.pdf \| https://www.accessdata.fda.gov/drugsatfda_docs/nda/2023/216386Orig1s000ClinPharmR.pdf#page=10 Page: 16.0	yes	no (co-administration study) Comment: Itraconazole did not result in a clinically relevant effect on the exposures of zavegepant. Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2023/216386Orig1s000PharmR.pdf \| https://www.accessdata.fda.gov/drugsatfda_docs/nda/2023/216386Orig1s000ClinPharmR.pdf#page=10 Page: 16.0
NTCP 22	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2023/216386Orig1s000ClinPharmR.pdf Page: 6 \| 10	yes	yes (co-administration study) Comment: Rifampicin showed 2.3-fold and 2.2-fold increase in zavegepant AUC and Cmax, respectively. Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2023/216386Orig1s000ClinPharmR.pdf Page: 6 \| 10
OATP1B3 435	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2023/216386Orig1s000ClinPharmR.pdf Page: 10.0	yes	yes (co-administration study) Comment: Rifampicin showed 2.3-fold and 2.2-fold increase in zavegepant AUC and Cmax, respectively. Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2023/216386Orig1s000ClinPharmR.pdf Page: 10.0

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 2263	inhibitor 2237 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2023/216386Orig1s000PharmR.pdf Page: 15.0

PubMed

Title	Date	PubMed
Zavegepant: First Approval.	2023 Jun	37227596

Patents

Sample Use Guides

In Vivo Use Guide

The recommended dose is 10 mg given as a single spray in one nostril, as needed. (2.1) • The maximum dose in a 24-hour period is 10 mg (one spray). (2.1)

Route of Administration: Nasal

In Vitro Use Guide

Vazegepant (BHV-3500) hydrochloride is a high affinity CGRP receptor antagonist (hCGRP Ki= 0.023 nM).

Name

Type

Language

ZAVEGEPANT

Official Name

English

BMS-742413

Preferred Name

English

ZAVEGEPANT [USAN]

Common Name

English

zavegepant [INN]

Common Name

English

VAZEGEPANT

Common Name

English

BHV-3500

Code

English

BMS-742413-01

Code

English

Zavegepant [WHO-DD]

Common Name

English

1-PIPERIDINECARBOXAMIDE, 4-(1,2-DIHYDRO-2-OXO-3-QUINOLINYL)-N-((1R)-1-((7-METHYL-1H-INDAZOL-5-YL)METHYL)-2-(4-(1-METHYL-4-PIPERIDINYL)-1-PIPERAZINYL)-2-OXOETHYL)-

Systematic Name

English

4-(1,2-DIHYDRO-2-OXO-3-QUINOLINYL)-N-((1R)-1-((7-METHYL-1H-INDAZOL-5-YL)METHYL)-2-(4-(1-METHYL-4-PIPERIDINYL)-1-PIPERAZINYL)-2-OXOETHYL)-1-PIPERIDINECARBOXAMIDE

Systematic Name

English

Code System Code Type Description

SMS_ID

300000028889