Orforglipron

Summary

Orforglipron (CHEMBL4446782) is a phase-3 clinical-stage small molecule targeting GLP1R; indicated across 3 conditions including type 2 diabetes mellitus and obesity disorder.

At a glance

• Status: Max clinical phase 3 (not approved)
• Modality: Small molecule
• Targets: 1 (GLP1R)
• Indications: 3 conditions
• Clinical trials: 46
• Chemistry: 883 Da · C48H48F2N10O5

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL4446782
Name	Orforglipron
Type	Small molecule
Max phase	3
FDA approved	no
PubChem CID	137319706
Molecular formula	C48H48F2N10O5
Molecular weight	883
InChIKey	USUWIEBBBWHKNI-KHIFEHGGSA-N

SMILES: C[C@H]1C[C@]1(C2=NOC(=O)N2)N3C4=C(C=C(C=C4)[C@H]5CCOC(C5)(C)C)C=C3C(=O)N6CCC7=NN(C(=C7[C@@H]6C)N8C=CN(C8=O)C9=C(C1=C(C=C9)N(N=C1)C)F)C1=CC(=C(C(=C1)C)F)C

IUPAC name: 3-[(1S,2S)-1-[5-[(4S)-2,2-dimethyloxan-4-yl]-2-[(4S)-2-(4-fluoro-3,5-dimethylphenyl)-3-[3-(4-fluoro-1-methylindazol-5-yl)-2-oxoimidazol-1-yl]-4-methyl-6,7-dihydro-4H-pyrazolo[4,3-c]pyridine-5-carbonyl]indol-1-yl]-2-methylcyclopropyl]-4H-1,2,4-oxadiazol-5-one

Also known as: LY-3502970, Ly3502970, LY3502970, Orforglipron, ORFORGLIPRON

Parent form; salt/anhydrous children: CHEMBL5314577

Patent coverage: 12 distinct patent families (59 SureChEMBL compound mentions), from 3 matched compound structure(s). 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
GLP1R	GLP-1 receptor	Partial agonist	8.49	0.2%	P43220

Broader ChEMBL bioactivity targets: 2 (assay-derived). Sample: Glucagon-like peptide 1 receptor, Glucagon-like peptide 1 receptor.

Bioactivity

ChEMBL activities: 4 potent at pChembl ≥ 5 of 4 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
GLP1R	8.92	EC50	1.2	nM	CHEMBL_ACT_26106923
GLP1R	8.92	EC50	1.2	nM	CHEMBL_ACT_28194959
O35659	6.52	EC50	300	nM	CHEMBL_ACT_19054407
GLP1R	6.22	EC50	600	nM	CHEMBL_ACT_19054382

Target pathways

Aggregated over 1 target gene(s): GLP1R.

Top Reactome pathways

3 total, by targets touching each:

Pathway	Targets	Genes
Glucagon-like Peptide-1 (GLP1) regulates insulin secretion	1	GLP1R
G alpha (s) signalling events	1	GLP1R
Glucagon-type ligand receptors	1	GLP1R

Dominant GO biological processes

GO term	Targets
cell surface receptor signaling pathway	1
adenylate cyclase-activating G protein-coupled receptor signaling pathway	1
activation of adenylate cyclase activity	1
positive regulation of cytosolic calcium ion concentration	1
learning or memory	1
regulation of heart contraction	1
post-translational protein targeting to membrane, translocation	1
negative regulation of blood pressure	1
positive regulation of blood pressure	1
hormone secretion	1
response to psychosocial stress	1
signal transduction	1
G protein-coupled receptor signaling pathway	1
regulation of biological quality	1
cellular response to glucagon stimulus	1

Indications & clinical

Indications

3 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
type 2 diabetes mellitus	3	MONDO:0005148	MONDO:0005148
obesity disorder	2	MONDO:0011122	EFO:0001073
hyperglycemia	1	MONDO:0002909	HP:0003074

Clinical trials

Total trials: 46.

Phase distribution

Phase	Trials
PHASE3	24
PHASE1	20
PHASE2	2

Top trials by phase / activity

NCT	Phase	Status	Title
NCT05869903	PHASE3	ACTIVE_NOT_RECRUITING	A Study of Orforglipron (LY3502970) in Adult Participants With Obesity or Overweight With Weight-Related Comorbidities
NCT06649045	PHASE3	ACTIVE_NOT_RECRUITING	A Master Protocol for Orforglipron in Participants With Obstructive Sleep Apnea and Obesity or Overweight
NCT06672549	PHASE3	RECRUITING	A Platform Trial for Pediatric Participants With Obesity or Overweight (LY900040)
NCT06672939	PHASE3	RECRUITING	A Study of Orforglipron (LY3502970) in Adolescent Participants With Obesity, or Overweight With Related Comorbidities
NCT06948422	PHASE3	ACTIVE_NOT_RECRUITING	A Master Protocol for Orforglipron (LY3502970) in Participants With Hypertension and Obesity or Overweight: (ATTAIN-Hypertension Screening)
NCT06948435	PHASE3	ACTIVE_NOT_RECRUITING	A Master Protocol Study of Orforglipron (LY3502970) in Participants With Hypertension and Obesity or Overweight (ATTAIN-Hypertension) GZL1
NCT06952530	PHASE3	ACTIVE_NOT_RECRUITING	A Master Protocol Study of Orforglipron (LY3502970) in Participants With Hypertension and Obesity or Overweight (ATTAIN-Hypertension) GZL2
NCT06972459	PHASE3	ACTIVE_NOT_RECRUITING	A Study of Orforglipron (LY3502970) in Participants With Obesity or Overweight and at Least One Weight-Related Comorbidity
NCT06972472	PHASE3	ACTIVE_NOT_RECRUITING	A Study of Orforglipron (LY3502970) in Participants With Obesity or Overweight and Type 2 Diabetes
NCT06993792	PHASE3	ACTIVE_NOT_RECRUITING	A Master Protocol for Orforglipron (LY3502970) in Participants With Obesity or Overweight With and Without Type 2 Diabetes
NCT07153471	PHASE3	RECRUITING	A Study of Orforglipron (LY3502970) in Participants With Obesity or Overweight and Osteoarthritis (OA) of the Knee
NCT07202884	PHASE3	RECRUITING	A Study of Orforglipron in Female Participants With Stress Urinary Incontinence Who Have Obesity or Overweight
NCT07223593	PHASE3	RECRUITING	Efficacy and Safety of Orforglipron in Participants With Peripheral Artery Disease
NCT07241390	PHASE3	RECRUITING	A Study of Orforglipron (LY3502970) on Cardiovascular Outcomes in Adults With Atherosclerotic Cardiovascular Disease and/or Chronic Kidney Disease (ATTAIN-Outcomes)
NCT07613307	PHASE3	NOT_YET_RECRUITING	A Study of Orforglipron (LY3502970) in Participants With Type 2 Diabetes Who Observe Ramadan Fasting
NCT05803421	PHASE3	COMPLETED	A Study of Daily Oral Orforglipron (LY3502970) Compared With Insulin Glargine in Participants With Type 2 Diabetes and Obesity or Overweight at Increased Cardiovascular Risk
NCT05872620	PHASE3	COMPLETED	A Study of Orforglipron in Adult Participants With Obesity or Overweight and Type 2 Diabetes
NCT05931380	PHASE3	COMPLETED	A Study of Once-Daily Oral Orforglipron (LY3502970) in Japanese Adult Participants With Obesity Disease
NCT05971940	PHASE3	COMPLETED	A Study of Orforglipron (LY3502970) in Adult Participants With Type 2 Diabetes and Inadequate Glycemic Control With Diet and Exercise Alone
NCT06010004	PHASE3	COMPLETED	A Long-term Safety Study of Orforglipron (LY3502970) in Participants With Type 2 Diabetes
NCT06045221	PHASE3	COMPLETED	A Study of Orforglipron (LY3502970) Compared With Semaglutide in Participants With Type 2 Diabetes Inadequately Controlled With Metformin
NCT06109311	PHASE3	COMPLETED	A Study of Orforglipron (LY3502970) in Participants With Type 2 Diabetes and Inadequate Glycemic Control With Insulin Glargine, With or Without Metformin and/or SGLT-2 Inhibitor
NCT06192108	PHASE3	COMPLETED	A Study of Orforglipron (LY3502970) Compared With Dapagliflozin in Adult Participants With Type 2 Diabetes and Inadequate Glycemic Control With Metformin
NCT06584916	PHASE3	COMPLETED	A Study of Orforglipron for the Maintenance of Body Weight Reduction in Participants Who Have Obesity or Overweight With Weight-Related Comorbidities (ATTAIN-MAINTAIN)
NCT05048719	PHASE2	COMPLETED	A Study of LY3502970 in Participants With Type 2 Diabetes Mellitus
NCT05051579	PHASE2	COMPLETED	A Study of LY3502970 in Participants With Obesity or Overweight With Weight-related Comorbidities
NCT03929744	PHASE1	COMPLETED	A Study of LY3502970 in Healthy Participants
NCT04426474	PHASE1	COMPLETED	A Study of LY3502970 in Participants With Type 2 Diabetes
NCT05051566	PHASE1	COMPLETED	A Multiple Dose Study of LY3502970 in Healthy Participants
NCT05086445	PHASE1	COMPLETED	A Study of LY3502970 in Japanese Participants With Type 2 Diabetes Mellitus
NCT05110794	PHASE1	COMPLETED	A Multiple-Dose Study of LY3502970 in Healthy Participants
NCT05313802	PHASE1	COMPLETED	A Study of LY3502970 in Healthy Overweight and Obese Participants
NCT05341089	PHASE1	COMPLETED	A Study of Two Different Formulations of LY3502970 in Healthy Participants
NCT05469126	PHASE1	COMPLETED	A Drug Interaction Study of Clarithromycin and LY3502970 in Healthy Participants
NCT05573230	PHASE1	COMPLETED	A Drug Interaction Study of Cyclosporine and LY3502970 in Healthy Participants
NCT05841238	PHASE1	COMPLETED	A Multiple Dose Study of LY3502970 in Healthy Overweight and Obese Participants
NCT05882032	PHASE1	COMPLETED	A Study of LY3502970 in Participants With Impaired and Normal Liver Function
NCT05936138	PHASE1	COMPLETED	A Study of LY3502970 in Participants With Normal and Impaired Renal Function
NCT06023095	PHASE1	COMPLETED	A Study of LY3502970 in Chinese Participants With Obesity or Are Overweight With Weight-related Comorbidities
NCT06085482	PHASE1	COMPLETED	A Phase I Study of LY3502970 in Healthy Participants

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.

17 molecules share ≥1 primary target. Top 17 by shared-target count:

Molecule	Source	Status	Shared targets
LIRAGLUTIDE	ChEMBL + PubChem	Phase 4 (approved)	GLP1R
DIHYDROERGOTAMINE	ChEMBL	Phase 4 (approved)	GLP1R
ELAGOLIX	ChEMBL	Phase 4 (approved)	GLP1R
EXENATIDE	ChEMBL	Phase 4 (approved)	GLP1R
GLUCAGON	ChEMBL	Phase 4 (approved)	GLP1R
LOPERAMIDE	ChEMBL	Phase 4 (approved)	GLP1R
PERPHENAZINE	ChEMBL	Phase 4 (approved)	GLP1R
SECRETIN	ChEMBL	Phase 4 (approved)	GLP1R
SEMAGLUTIDE	ChEMBL	Phase 4 (approved)	GLP1R
TIRZEPATIDE	ChEMBL	Phase 4 (approved)	GLP1R
TOLVAPTAN	ChEMBL	Phase 4 (approved)	GLP1R
COTADUTIDE	ChEMBL	Phase 2	GLP1R
DANUGLIPRON	ChEMBL	Phase 2	GLP1R
DEVAZEPIDE	ChEMBL	Phase 2	GLP1R
GLP-1	ChEMBL	Phase 2	GLP1R
LOTIGLIPRON	ChEMBL	Phase 2	GLP1R
PF-06291874	ChEMBL	Phase 2	GLP1R