Mitapivat

Summary

Mitapivat (CHEMBL4299940) is an approved small molecule (ATC B06AX04) targeting PKM and PKLR; indicated across 5 conditions including alpha thalassemia spectrum and beta thalassemia.

At a glance

• Status: Approved (max clinical phase 4)
• Modality: Small molecule
• ATC class: B06AX04
• Targets: 2 (PKM, PKLR)
• Indications: 5 conditions
• Clinical trials: 26
• Chemistry: 450.6 Da · C24H26N4O3S

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL4299940
Name	Mitapivat
Type	Small molecule
Max phase	4
FDA approved	yes
PubChem CID	59634741
ATC	B06AX04
Molecular formula	C24H26N4O3S
Molecular weight	450.6
InChIKey	XAYGBKHKBBXDAK-UHFFFAOYSA-N

SMILES: C1CC1CN2CCN(CC2)C(=O)C3=CC=C(C=C3)NS(=O)(=O)C4=CC=CC5=C4N=CC=C5

IUPAC name: N-[4-[4-(cyclopropylmethyl)piperazine-1-carbonyl]phenyl]quinoline-8-sulfonamide

Also known as: Ag-348, AG-348, Mitapivat, Pkr-in-1, MITAPIVAT

Parent form; salt/anhydrous children: CHEMBL4297223

Patent coverage: 85 distinct patent families (236 SureChEMBL compound mentions), from 2 matched compound structure(s). One matched structure accounts for 233 (99%) of the total. Mentions count patents naming the compound (not distinct inventions), so promiscuous / reference molecules inflate the mention figure — families are the dedup metric.

Targets

Targets

Primary targets (GtoPdb curated mechanism): the Cancer dependency column is the DepMap CRISPR fitness signal (% of screened cell lines dependent on the target).

Gene	Target	Action	pAffinity	Cancer dependency	UniProt
PKM	pyruvate kinase M1/2	Activation	7	87.7%	P14618
PKLR	pyruvate kinase L/R	Positive		1.4%	P30613

Broader ChEMBL bioactivity targets: 2 (assay-derived). Sample: Pyruvate kinase PKLR, Pyruvate kinase PKM.

Bioactivity

ChEMBL activities: 5 potent at pChembl ≥ 5 of 5 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
PKM	7.7	EC50	20	nM	CHEMBL_ACT_25932823
PKM	7.7	IC50	20	nM	CHEMBL_ACT_26123571
PKLR	7.54	AC50	29	nM	CHEMBL_ACT_22758020
PKM	7.43	EC50	37	nM	CHEMBL_ACT_24813525
PKM	7.21	AC50	62	nM	CHEMBL_ACT_26123587

Target pathways

Aggregated over 2 target gene(s): PKM, PKLR.

Top Reactome pathways

10 total, by targets touching each:

Pathway	Targets	Genes
Glycolysis	2	PKLR, PKM
Pyruvate metabolism	2	PKLR, PKM
ChREBP activates metabolic gene expression	1	PKLR
Innate Immune System	1	PKM
Immune System	1	PKM
Regulation of gene expression in beta cells	1	PKLR
Neutrophil degranulation	1	PKM
SARS-CoV-1-host interactions	1	PKLR
Negative Regulation of CDH1 Gene Transcription	1	PKM
Regulation of pyruvate metabolism	1	PKM

Dominant GO biological processes

GO term	Targets
glycolytic process	2
cellular response to insulin stimulus	2
programmed cell death	1
positive regulation of transcription by RNA polymerase II	1
canonical glycolysis	1
positive regulation of sprouting angiogenesis	1
positive regulation of cytoplasmic translation	1
chromatin remodeling	1
regulation of translation	1
response to hypoxia	1
response to nutrient	1
response to glucose	1
response to metal ion	1
response to ATP	1
pyruvate biosynthetic process	1

Indications & clinical

Indications

5 indications (0 at ChEMBL trial phase 4). Phase below is the highest clinical-trial phase recorded for this drug against each disease — not the molecule’s overall approval status (that is in the Summary).

Indication	Trial phase	MONDO	EFO
alpha thalassemia spectrum	3	MONDO:0011399	Orphanet:846
beta thalassemia	3	MONDO:0019402	Orphanet:848
thalassemia	2	MONDO:0000984	EFO:1001996
sickle cell disease	2	MONDO:0011382	MONDO:0011382
liver disorder	1	MONDO:0005154	EFO:0001421

Clinical trials

Total trials: 26.

Phase distribution

Phase	Trials
PHASE3	9
PHASE1	9
PHASE2	4
PHASE4	1
PHASE2/PHASE3	1
PHASE1/PHASE2	1
EARLY_PHASE1	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT05777993	PHASE4	ENROLLING_BY_INVITATION	A Study to Provide Continued Access to Mitapivat for Participants Who Previously Completed an Agios-Sponsored Mitapivat Study
NCT04770753	PHASE3	ACTIVE_NOT_RECRUITING	A Study Evaluating the Efficacy and Safety of Mitapivat in Participants With Non-Transfusion-Dependent Alpha- or Beta-Thalassemia (α- or β-NTDT)
NCT04770779	PHASE3	ACTIVE_NOT_RECRUITING	A Study Evaluating the Efficacy and Safety of Mitapivat in Participants With Transfusion-Dependent Alpha- or Beta-Thalassemia (α- or β-TDT)
NCT05031780	PHASE2/PHASE3	ACTIVE_NOT_RECRUITING	A Study Evaluating the Efficacy and Safety of Mitapivat (AG-348) in Participants With Sickle Cell Disease (RISE UP)
NCT05144256	PHASE3	ACTIVE_NOT_RECRUITING	A Study to Evaluate the Efficacy and Safety of Mitapivat in Pediatric Participants With Pyruvate Kinase Deficiency (PKD) Who Are Regularly Transfused, Followed by a 5-Year Extension Period
NCT05175105	PHASE3	ACTIVE_NOT_RECRUITING	A Study to Evaluate the Efficacy and Safety of Mitapivat in Pediatric Participants With Pyruvate Kinase Deficiency (PKD) Who Are Not Regularly Transfused, Followed by a 5-Year Extension Period
NCT07506863	PHASE3	NOT_YET_RECRUITING	A Study to Investigate the Efficacy, Pharmacokinetics, and Safety of Mitapivat in Pediatric Participants With Transfusion-Dependent Alpha- or Beta-Thalassemia (α- or β-TDT)
NCT07517133	PHASE3	NOT_YET_RECRUITING	A Study to Investigate the Efficacy, Pharmacokinetics, and Safety of Mitapivat in Pediatric Participants With α- or β-Non-Transfusion-Dependent Thalassemia
NCT03548220	PHASE3	COMPLETED	A Study to Evaluate Efficacy and Safety of AG-348 in Not Regularly Transfused Adult Participants With Pyruvate Kinase Deficiency (PKD)
NCT03559699	PHASE3	COMPLETED	A Study Evaluating the Efficacy and Safety of AG-348 in Regularly Transfused Adult Participants With Pyruvate Kinase Deficiency (PKD)
NCT03853798	PHASE3	COMPLETED	Extension Study of AG-348 in Adult Participants With Pyruvate Kinase Deficiency Previously Enrolled in AG-348-006 or AG348-C-007
NCT03692052	PHASE2	ACTIVE_NOT_RECRUITING	A Study to Determine the Efficacy, Safety, Pharmacokinetics, and Pharmacodynamics of AG-348 in Adult Participants With Non-transfusion-dependent Thalassemia
NCT04610866	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Long-term Mitapivat Dosing in Subjects With Stable Sickle Cell Disease: An Extension of a Phase I Pilot Study of Mitapivat
NCT07055243	PHASE2	RECRUITING	To Assess Safety of Mitapivat and Provide Proof of Concept of the Efficacy of the Drug in Patients With RBC Membranopathies or CDAII.
NCT02476916	PHASE2	COMPLETED	A Study of AG-348 in Adult Participants With Pyruvate Kinase (PK) Deficiency
NCT06286046	PHASE2	WITHDRAWN	A Study of Mitapivat in Participants With Sickle Cell Disease and Nephropathy
NCT02108106	PHASE1	COMPLETED	A Phase I Study of AG-348 in Healthy Volunteers
NCT02149966	PHASE1	COMPLETED	A Phase I Study of AG-348 in Healthy Volunteers
NCT03250598	PHASE1	COMPLETED	Study to Evaluate the Pharmacokinetics, Safety, and QTc Effect of AG-348 in Healthy Subjects of Japanese Origin and Non-Asian Origin
NCT03703505	PHASE1	COMPLETED	A Study to Evaluate the Absorption, Distribution, Metabolism, Excretion and Absolute Bioavailability of AG-348 in Healthy Male Participants Following Administration of a Single Oral Dose of [14C]AG-348 and Concomitant Single Intravenous Microdose of [13C6]AG-348
NCT04472832	PHASE1	COMPLETED	A Study to Evaluate the Pharmacokinetics, Safety, and Tolerability of Mitapivat (AG-348) in Healthy Adult Participants
NCT04565678	PHASE1	COMPLETED	A Study to Assess the Relative Bioavailability and Effect of Food on the Coated Granule Formulation of Mitapivat in Healthy Participants
NCT04696393	PHASE1	COMPLETED	A Study to Compare the Pharmacokinetics and Safety of Mitapivat 100 mg Tablet Formulation With Mitapivat 2 × 50 mg Tablet Formulation in Healthy Adult Participants
NCT05610657	PHASE1	COMPLETED	A Pharmacokinetic Study of Mitapivat in Participants With Moderate Hepatic Impairment Compared to Matched Healthy Control Participants With Normal Hepatic Function
NCT06648824	PHASE1	COMPLETED	Study of How Mitapivat Affects Midazolam Blood Levels in Healthy Participants
NCT04000165	EARLY_PHASE1	COMPLETED	A Dose-Finding Study of AG-348 in Sickle Cell Disease

Clinical evidence (CIViC)

No CIViC predictive evidence (expected for non-precision-medicine drugs).

Pharmacology

Pharmacogenomics

No CPIC/DPWG dosing guideline or drug-level clinical/variant annotations in PharmGKB for this molecule.

Related molecules

Related molecules

Molecules sharing ≥1 of this drug’s curated primary targets, merged from two biobtree sources and ranked by shared-target count, then clinical phase: ChEMBL clinical-stage candidates (development phase ≥2) and PubChem drug-class bioactivity (approved / known drugs acting on the target). Deduplicated by drug name; the drug’s own salt forms are excluded. Note: for a drug with few primary targets a shared-target match can reflect off-target / promiscuous binding rather than the same therapeutic mechanism — the phase ordering surfaces bona-fide therapeutics first.

69 molecules share ≥1 primary target. Top 60 by shared-target count:

Molecule	Source	Status	Shared targets
SURAMIN	ChEMBL	Phase 3	PKLR, PKM
MENADIONE	ChEMBL + PubChem	Phase 4 (approved)	PKM
NALIDIXIC ACID	ChEMBL + PubChem	Phase 4 (approved)	PKM
SIROLIMUS	ChEMBL + PubChem	Phase 4 (approved)	PKM
ACEMETACIN	ChEMBL	Phase 4 (approved)	PKM
AMLEXANOX	ChEMBL	Phase 4 (approved)	PKM
APOMORPHINE	ChEMBL	Phase 4 (approved)	PKM
BENZTHIAZIDE	ChEMBL	Phase 4 (approved)	PKM
BIOTIN	ChEMBL	Phase 4 (approved)	PKM
CEFUROXIME	ChEMBL	Phase 4 (approved)	PKM
DISULFIRAM	ChEMBL	Phase 4 (approved)	PKM
DITHIAZANINE IODIDE	ChEMBL	Phase 4 (approved)	PKM
ETHOXZOLAMIDE	ChEMBL	Phase 4 (approved)	PKM
FELBAMATE	ChEMBL	Phase 4 (approved)	PKM
HYDRALAZINE	ChEMBL	Phase 4 (approved)	PKM
INDOPROFEN	ChEMBL	Phase 4 (approved)	PKM
MECAMYLAMINE	ChEMBL	Phase 4 (approved)	PKM
METHYLENE BLUE	ChEMBL	Phase 4 (approved)	PKM
MITOXANTRONE	ChEMBL	Phase 4 (approved)	PKM
MOXISYLYTE	ChEMBL	Phase 4 (approved)	PKM
NICLOSAMIDE	ChEMBL	Phase 4 (approved)	PKM
NITAZOXANIDE	ChEMBL	Phase 4 (approved)	PKM
OMEPRAZOLE	ChEMBL	Phase 4 (approved)	PKM
PENTAMIDINE ISETHIONATE	ChEMBL	Phase 4 (approved)	PKM
PSEUDOEPHEDRINE	ChEMBL	Phase 4 (approved)	PKM
RABEPRAZOLE	ChEMBL	Phase 4 (approved)	PKM
RILUZOLE	ChEMBL	Phase 4 (approved)	PKM
SULFADIAZINE, SILVER	ChEMBL	Phase 4 (approved)	PKM
TRIAMTERENE	ChEMBL	Phase 4 (approved)	PKM
TRIFLUPERIDOL	ChEMBL	Phase 4 (approved)	PKM
ZIDOVUDINE	ChEMBL	Phase 4 (approved)	PKM
PHENYLALANINE	ChEMBL + PubChem	Phase 3 (approved)	PKM
CURCUMIN	ChEMBL	Phase 3	PKM
DIACEREIN	ChEMBL	Phase 3	PKM
EBSELEN	ChEMBL	Phase 3	PKM
EPIGALOCATECHIN GALLATE	ChEMBL	Phase 3	PKM
SPERMIDINE	ChEMBL	Phase 3	PKM
SURAMIN HEXASODIUM	ChEMBL	Phase 3	PKM
TRANILAST	ChEMBL	Phase 3	PKM
(-)-EPICATECHIN	ChEMBL	Phase 2	PKM
BENZOYLPAS	ChEMBL	Phase 2	PKM
CLEMIZOLE	ChEMBL	Phase 2	PKM
DAIDZEIN	ChEMBL	Phase 2	PKM
DEXEFAROXAN	ChEMBL	Phase 2	PKM
DIHYDREXIDINE	ChEMBL	Phase 2	PKM
ELLAGIC ACID	ChEMBL	Phase 2	PKLR
ESOXYBUTYNIN	ChEMBL	Phase 2	PKM
FISETIN	ChEMBL	Phase 2	PKM
FOSFRUCTOSE	ChEMBL	Phase 2	PKM
GENISTEIN	ChEMBL	Phase 2	PKM
ISOQUERCETIN	ChEMBL	Phase 2	PKM
NIFLUMIC ACID	ChEMBL	Phase 2	PKM
OXATOMIDE	ChEMBL	Phase 2	PKM
PIRENPERONE	ChEMBL	Phase 2	PKM
RITANSERIN	ChEMBL	Phase 2	PKM
SANGUINARIUM	ChEMBL	Phase 2	PKM
TENONITROZOLE	ChEMBL	Phase 2	PKM
THIRAM	ChEMBL	Phase 2	PKM
cyclosporine	PubChem	Approved	PKM
cysteine	PubChem	Approved	PKM