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Also known as: Qulipta, Mk-8031, 1374248-81-3, Agn-241689, Atogepant [inn], Atogepant [who-dd]
Molecular Formula
C29H23F6N5O3
Molecular Weight
603.5  g/mol
InChI Key
QIVUCLWGARAQIO-OLIXTKCUSA-N
FDA UNII
7CRV8RR151

Atogepant
Atogepant is an oral antagonist of calcitonin gene-related peptide (CGRP) receptors indicated for the prevention of episodic migraine headaches. It was developed by AbbVie and received FDA approval under the brand name Qulipta in September 2021. While its approval was predated by two other members of the same drug family, namely [ubrogepant] and [rimegepant], these agents are indicated only for abortive migraine therapy - atogepant is novel in that it is the first and only oral CGRP antagonist approved for preventative use in migraine. In patients requiring preventative migraine therapy, current practice guidelines recommend the use of certain anti-epileptic medications (e.g. [valproic acid] or [topiramate]) or beta-blockers (e.g. [propranolol]), all of which can be associated with significant adverse effects. The "gepants" family of drugs, including atogepant, are comparatively well-tolerated and may provide a desirable treatment option for patients struggling with adverse reactions to other preventative therapies.
Atogepant is a Calcitonin Gene-related Peptide Receptor Antagonist. The mechanism of action of atogepant is as a Calcitonin Gene-related Peptide Receptor Antagonist.
1 2D Structure

Atogepant

2 Identification
2.1 Computed Descriptors
2.1.1 IUPAC Name
(3S)-N-[(3S,5S,6R)-6-methyl-2-oxo-1-(2,2,2-trifluoroethyl)-5-(2,3,6-trifluorophenyl)piperidin-3-yl]-2-oxospiro[1H-pyrrolo[2,3-b]pyridine-3,6'-5,7-dihydrocyclopenta[b]pyridine]-3'-carboxamide
2.1.2 InChI
InChI=1S/C29H23F6N5O3/c1-13-16(22-18(30)4-5-19(31)23(22)32)8-20(26(42)40(13)12-29(33,34)35)38-25(41)15-7-14-9-28(10-21(14)37-11-15)17-3-2-6-36-24(17)39-27(28)43/h2-7,11,13,16,20H,8-10,12H2,1H3,(H,38,41)(H,36,39,43)/t13-,16-,20+,28+/m1/s1
2.1.3 InChI Key
QIVUCLWGARAQIO-OLIXTKCUSA-N
2.1.4 Canonical SMILES
CC1C(CC(C(=O)N1CC(F)(F)F)NC(=O)C2=CC3=C(CC4(C3)C5=C(NC4=O)N=CC=C5)N=C2)C6=C(C=CC(=C6F)F)F
2.1.5 Isomeric SMILES
C[C@@H]1[C@@H](C[C@@H](C(=O)N1CC(F)(F)F)NC(=O)C2=CC3=C(C[C@@]4(C3)C5=C(NC4=O)N=CC=C5)N=C2)C6=C(C=CC(=C6F)F)F
2.2 Other Identifiers
2.2.1 UNII
7CRV8RR151
2.3 Synonyms
2.3.1 MeSH Synonyms

1. (3s)-n-((3s,5s,6r)-6-methyl-2-oxo-1-(2,2,2-trifluoroethyl)-5-(2,3,6-trifluorophenyl)piperidin-3-yl)-2-oxospiro(1h-pyrrolo(2,3-b)pyridine-3,6'-5,7-dihydrocyclopenta(b)pyridine)-3'-carboxamide

2.3.2 Depositor-Supplied Synonyms

1. Qulipta

2. Mk-8031

3. 1374248-81-3

4. Agn-241689

5. Atogepant [inn]

6. Atogepant [who-dd]

7. 7crv8rr151

8. Atogepant (usan)

9. Atogepant [usan]

10. (3's)-1',2',5,7-tetrahydro-n-((3s,5s,6r)-6-methyl-2-oxo-1-(2,2,2-trifluoroethyl)-5-(2,3,6-trifluorophenyl)-3-piperidinyl)-2'-oxospiro(6h-cyclopenta(b)pyridine-6,3'-(3h)pyrrolo(2,3-b)pyridine)-3-carboxamide

11. (3's)-n-[(3s,5s,6r)-6-methyl-2-oxo-1-(2,2,2-trifluoroethyl)-5-(2,3,6-trifluorophenyl)piperidin-3-yl]-2'-oxo-1',2',5,7-tetrahydrospiro[cyclopenta[b]pyridine-6,3'-pyrrolo[2,3-b]pyridine]-3-carboxamide

12. (3s)-n-[(3s,5s,6r)-6-methyl-2-oxo-1-(2,2,2-trifluoroethyl)-5-(2,3,6-trifluorophenyl)piperidin-3-yl]-2-oxospiro[1h-pyrrolo[2,3-b]pyridine-3,6'-5,7-dihydrocyclopenta[b]pyridine]-3'-carboxamide

13. Spiro(6h-cyclopenta(b)pyridine-6,3'-(3h)pyrrolo(2,3-b)pyridine)-3-carboxamide, 1',2',5,7-tetrahydro-n-((3s,5s,6r)-6-methyl-2-oxo-1-(2,2,2-trifluoroethyl)-5-(2,3,6-trifluorophenyl)-3-piperidinyl)-2'-oxo-, (3's)-

14. Atogepant [usan:inn]

15. Unii-7crv8rr151

16. Gtpl9730

17. Schembl4570348

18. Atogepant [orange Book]

19. Chembl3991065

20. Dtxsid901337079

21. Bcp29018

22. Ex-a6847

23. Mk 8031; Mk8031; Atogepant

24. Example 4 [us20120122911]

25. Hy-109022

26. Cs-0030524

27. D11313

2.4 Create Date
2013-12-02
3 Chemical and Physical Properties
Molecular Weight 603.5 g/mol
Molecular Formula C29H23F6N5O3
XLogP33.4
Hydrogen Bond Donor Count2
Hydrogen Bond Acceptor Count11
Rotatable Bond Count4
Exact Mass603.17050859 g/mol
Monoisotopic Mass603.17050859 g/mol
Topological Polar Surface Area104 Ų
Heavy Atom Count43
Formal Charge0
Complexity1110
Isotope Atom Count0
Defined Atom Stereocenter Count4
Undefined Atom Stereocenter Count0
Defined Bond Stereocenter Count0
Undefined Bond Stereocenter Count0
Covalently Bonded Unit Count1
4 Drug and Medication Information
4.1 Drug Indication

Atogepant is indicated for the prevention of episodic migraine in adults.


Prevention of migraine headaches


5 Pharmacology and Biochemistry
5.1 Pharmacology

Atogepant helps to prevent migraine headaches by antagonizing the activity of a pronociceptive molecule (CGRP) which has been implicated in migraine pathophysiology. Intended for preventative use, rather than abortive migraine therapy, atogepant is administered once daily. While no dose adjustments are required for patients with mild or moderate hepatic impairment, atogepant should be avoided in patients with severe hepatic impairment. Similarly, no dose adjustments are required for patients with mild or moderate renal impairment, but patients with severe renal impairment should be limited to a maximum daily dose of 10mg.


5.2 FDA Pharmacological Classification
5.2.1 Active Moiety
ATOGEPANT
5.2.2 FDA UNII
7CRV8RR151
5.2.3 Pharmacological Classes
Calcitonin Gene-related Peptide Receptor Antagonists [MoA]; Calcitonin Gene-related Peptide Receptor Antagonist [EPC]
5.3 ATC Code

N - Nervous system

N02 - Analgesics

N02C - Antimigraine preparations

N02CD - Calcitonin gene-related peptide (cgrp) antagonists

N02CD07 - Atogepant


5.4 Absorption, Distribution and Excretion

Absorption

The time to peak plasma concentration following oral administration is approximately 2-3 hours. Atogepant displays dose-proportional pharmacokinetics up to approximately 3-fold its recommended maximum dosage, and its pharmacokinetics are not significantly influenced by co-administration with food.


Route of Elimination

The elimination of atogepant occurs primarily via metabolism by CYP3A4. Following a single oral dose of radiolabeled atogepant to healthy male subjects, 42% of the administered dose was recovered as unchanged parent drug in the feces and 5% as unchanged parent drug in the urine. In total, approximately 81% of the radioactivity was recovered in the feces, with only 8% recovered in the urine.


Volume of Distribution

The mean apparent volume of distribution of atogepant is 292 L.


Clearance

The mean apparent oral clearance of atogepant is approximately 19 L/h.


5.5 Metabolism/Metabolites

The metabolism of atogepant is mediated primarily via CYP3A4. The most prevalent circulating compounds in plasma are atogepant itself and a glucuronide conjugate metabolite (M23), comprising approximately 75% and 15% of the administered dose, respectively, with at least 10 other metabolites detected in feces representing <10% of the administered dose.


5.6 Biological Half-Life

The elimination half-life of atogepant following oral administration is approximately 11 hours.


5.7 Mechanism of Action

The currently accepted theory of migraine pathophysiology considers dysfunction of the central nervous system, in particular the trigeminal ganglion, to be the root cause behind the condition. Activation of the trigeminal ganglion triggers the stimulation of trigeminal afferents that project to the spinal cord and synapse on various pain-sensing intra- and extracranial structures, such as the dura mater. Pain signals are then further transmitted via second-order ascending neurons to the brainstem, hypothalamus, and thalamic nuclei, and from there to several cortical regions (e.g. auditory, visual, motor cortices). The trigeminal ganglion appears to amplify and perpetuate the migraine headache pain through the activation of perivascular fibers and the release of molecules involved in pain generation, such as calcitonin gene-related peptide (CGRP). The -isoform of CGRP, expressed in primary sensory neurons, is a potent vasodilator and has been implicated in migraine pathogenesis - CGRP levels are acutely elevated during migraine attacks, return to normal following treatment with triptan medications, and intravenous infusions of CGRP have been shown to trigger migraine-like headaches in migraine patients. In addition to its vasodilatory properties, CGRP appears to be a pronociceptive factor that modulates neuronal excitability to facilitate pain responses. Atogepant is an antagonist of the calcitonin gene-related peptide receptor - it competes with CGRP for occupancy at these receptors, preventing the actions of CGRP and its ability to induce and perpetuate migraine headache pain.


API SUPPLIERS

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Metrochem API Private Limited

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Micro Labs Limited

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Micro Labs Limited

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FDA Orange Book

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ABBVIE

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ATOGEPANT

Brand Name : QULIPTA

Dosage Form : TABLET;ORAL

Dosage Strength : 10MG

Approval Date : 2021-09-28

Application Number : 215206

RX/OTC/DISCN : RX

RLD : Yes

TE Code :

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ATOGEPANT

Brand Name : QULIPTA

Dosage Form : TABLET;ORAL

Dosage Strength : 30MG

Approval Date : 2021-09-28

Application Number : 215206

RX/OTC/DISCN : RX

RLD : Yes

TE Code :

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ATOGEPANT

Brand Name : QULIPTA

Dosage Form : TABLET;ORAL

Dosage Strength : 60MG

Approval Date : 2021-09-28

Application Number : 215206

RX/OTC/DISCN : RX

RLD : Yes

TE Code :

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Europe

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Atogepant

Brand Name : Aquipta

Dosage Form : Tablet

Dosage Strength : 60 mg

Packaging : Blisterpakning 28item

Approval Date :

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Regulatory Info :

Registration Country : Norway

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Atogepant

Brand Name : Aquipta

Dosage Form : Tablet

Dosage Strength : 10 mg

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Registration Country : Norway

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Atogepantum

Brand Name : Aquipta

Dosage Form : Tablet

Dosage Strength : 10mg

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Registration Country : Switzerland

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Atogepantum

Brand Name : Aquipta

Dosage Form : Tablet

Dosage Strength : 60mg

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Registration Country : Switzerland

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ATOGEPANT

Brand Name : QULIPTA

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Dosage Strength : 10MG

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Application Number : 2533979

Regulatory Info : Prescription

Registration Country : Canada

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ATOGEPANT

Brand Name : QULIPTA

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Dosage Strength : 30MG

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Application Number : 2533987

Regulatory Info : Prescription

Registration Country : Canada

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ATOGEPANT

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Application Number : 2533995

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US Patents

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ATOGEPANT

US Patent Number : 9850246

Drug Substance Claim : Y

Drug Product Claim :

Application Number : 215206

Patent Use Code :

Delist Requested :

Patent Use Description :

Patent Expiration Date : 2033-03-13

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ATOGEPANT

US Patent Number : 9499545

Drug Substance Claim : Y

Drug Product Claim : Y

Application Number : 215206

Patent Use Code : U-3534

Delist Requested :

Patent Use Description :

Patent Expiration Date : 2031-11-10

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ATOGEPANT

US Patent Number : 9850246

Drug Substance Claim : Y

Drug Product Claim :

Application Number : 215206

Patent Use Code :

Delist Requested :

Patent Use Description :

Patent Expiration Date : 2033-03-13

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ATOGEPANT

US Patent Number : 9499545

Drug Substance Claim : Y

Drug Product Claim : Y

Application Number : 215206

Patent Use Code : U-3534

Delist Requested :

Patent Use Description :

Patent Expiration Date : 2031-11-10

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ATOGEPANT

US Patent Number : 10117836

Drug Substance Claim :

Drug Product Claim : Y

Application Number : 215206

Patent Use Code :

Delist Requested :

Patent Use Description :

Patent Expiration Date : 2035-01-30

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ATOGEPANT

US Patent Number : 9499545

Drug Substance Claim : Y

Drug Product Claim : Y

Application Number : 215206

Patent Use Code : U-3534

Delist Requested :

Patent Use Description :

Patent Expiration Date : 2031-11-10

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ATOGEPANT

US Patent Number : 10117836

Drug Substance Claim :

Drug Product Claim : Y

Application Number : 215206

Patent Use Code :

Delist Requested :

Patent Use Description :

Patent Expiration Date : 2035-01-30

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ATOGEPANT

US Patent Number : 8754096

Drug Substance Claim : Y

Drug Product Claim : Y

Application Number : 215206

Patent Use Code : U-3534

Delist Requested :

Patent Use Description :

Patent Expiration Date : 2032-07-19

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ABBVIE

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ATOGEPANT

US Patent Number : 10117836

Drug Substance Claim :

Drug Product Claim : Y

Application Number : 215206

Patent Use Code :

Delist Requested :

Patent Use Description :

Patent Expiration Date : 2035-01-30

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ABBVIE

U.S.A
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Medlab Asia & Asia Health
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ATOGEPANT

US Patent Number : 8754096

Drug Substance Claim : Y

Drug Product Claim : Y

Application Number : 215206

Patent Use Code : U-3534

Delist Requested :

Patent Use Description :

Patent Expiration Date : 2032-07-19

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