Pramlintide

Summary

Pramlintide (CHEMBL2103758) is an approved protein (ATC A10BX05) targeting CALCR; indicated across 4 conditions including diabetes mellitus and type 1 diabetes mellitus.

At a glance

• Status: Approved (max clinical phase 4)
• Modality: Protein
• ATC class: A10BX05
• Targets: 1 (CALCR)
• Indications: 4 conditions
• Clinical trials: 24
• Chemistry: 3949 Da · C171H267N51O53S2

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL2103758
Name	Pramlintide
Type	Protein
Max phase	4
FDA approved	yes
PubChem CID	70691388
ATC	A10BX05
Molecular formula	C171H267N51O53S2
Molecular weight	3949
InChIKey	TZIRZGBAFTZREM-MKAGXXMWSA-N

SMILES: CC[C@H](C)[C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N1CCC[C@H]1C(=O)N2CCC[C@H]2C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(=O)N)C(=O)N[C@@H](C(C)C)C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(=O)N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC3=CC=C(C=C3)O)C(=O)N)NC(=O)[C@@H]4CCCN4C(=O)CNC(=O)[C@H](CC5=CC=CC=C5)NC(=O)[C@H](CC(=O)N)NC(=O)[C@H](CC(=O)N)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@H](CC6=CNC=N6)NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC7=CC=CC=C7)NC(=O)[C@H](CC(=O)N)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCC(=O)N)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](C)NC(=O)[C@@H]8CSSC[C@@H](C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@H](C(=O)N8)[C@@H](C)O)C)[C@@H](C)O)CC(=O)N)NC(=O)[C@H](CCCCN)N

IUPAC name: (2S)-N-[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-4-amino-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-4-amino-1-[[(2S)-4-amino-1-[[(2S)-1-[[2-[(2S)-2-[[(2S,3S)-1-[[(2S)-1-[(2S)-2-[(2S)-2-[[(2S,3R)-1-[[(2S)-4-amino-1-[[(2S)-1-[[2-[[(2S)-1-[[(2S)-4-amino-1-[[(2S,3R)-1-[[(2S)-1-amino-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-3-hydroxy-1-oxobutan-2-yl]amino]-1,4-dioxobutan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-2-oxoethyl]amino]-3-methyl-1-oxobutan-2-yl]amino]-1,4-dioxobutan-2-yl]amino]-3-hydroxy-1-oxobutan-2-yl]carbamoyl]pyrrolidine-1-carbonyl]pyrrolidin-1-yl]-4-methyl-1-oxopentan-2-yl]amino]-3-methyl-1-oxopentan-2-yl]carbamoyl]pyrrolidin-1-yl]-2-oxoethyl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-1,4-dioxobutan-2-yl]amino]-1,4-dioxobutan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-3-(1H-imidazol-4-yl)-1-oxopropan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-1,4-dioxobutan-2-yl]amino]-1-oxopropan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]-2-[[(2S,3R)-2-[[(2S)-2-[[(4R,7S,10S,13S,16S,19R)-16-(2-amino-2-oxoethyl)-19-[[(2S)-2,6-diaminohexanoyl]amino]-7,13-bis[(1R)-1-hydroxyethyl]-10-methyl-6,9,12,15,18-pentaoxo-1,2-dithia-5,8,11,14,17-pentazacycloicosane-4-carbonyl]amino]propanoyl]amino]-3-hydroxybutanoyl]amino]pentanediamide

Also known as: AC-0137, AC-137, AC0137, AC137, Pramlintida, Pramlintide, Tripro-amylin, PRAMLINTIDE

Parent form; salt/anhydrous children: CHEMBL3833353

Patent coverage: 390 distinct patent families (883 SureChEMBL compound mentions), from 1 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
CALCR	CT receptor	Agonist	8.26	0%	P30988
	AMY1 receptor	Agonist	9.45
	AMY2 receptor	Agonist	8.86
	AMY3 receptor	Agonist	9.28

Broader ChEMBL bioactivity targets: 8 (assay-derived). Sample: Calcitonin receptor, Calcitonin-gene-related peptide receptor, CALCRL/RAMP1, Amylin receptor AMY3; CALCR/RAMP3, Amylin receptor AMY1, CALCR/RAMP1, Amylin receptor AMY3; CALCR/RAMP3, Adrenomedullin receptor, AM2; CALCRL/RAMP3, Calcitonin receptor, Amylin receptor AMY2; CALCR/RAMP2.

Bioactivity

ChEMBL activities: 12 potent at pChembl ≥ 5 of 12 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
RAMP1	10.66	EC50	0.02	nM	CHEMBL_ACT_25914943
RAMP3	10.53	EC50	0.03	nM	CHEMBL_ACT_25914951
RAMP2	10.19	EC50	0.06	nM	CHEMBL_ACT_25914947
CALCR	10.15	EC50	0.07	nM	CHEMBL_ACT_25914533
RAMP3	9.94	IC50	0.11	nM	CHEMBL_ACT_25914609
P32214	9.91	IC50	0.12	nM	CHEMBL_ACT_25914663
CALCR	9.48	EC50	0.33	nM	CHEMBL_ACT_25914939
CALCR	8.83	IC50	1.49	nM	CHEMBL_ACT_25914627
P32214	8.74	EC50	1.82	nM	CHEMBL_ACT_25914589
P32214	8.23	IC50	5.83	nM	CHEMBL_ACT_25914681
RAMP1	7.63	EC50	23.44	nM	CHEMBL_ACT_25914955
RAMP3	6.83	EC50	147.9	nM	CHEMBL_ACT_25914963

Target pathways

Aggregated over 1 target gene(s): CALCR.

Top Reactome pathways

7 total, by targets touching each:

Pathway	Targets	Genes
Signal Transduction	1	CALCR
Signaling by GPCR	1	CALCR
Class B/2 (Secretin family receptors)	1	CALCR
GPCR downstream signalling	1	CALCR
G alpha (s) signalling events	1	CALCR
Calcitonin-like ligand receptors	1	CALCR
GPCR ligand binding	1	CALCR

Dominant GO biological processes

GO term	Targets
ossification	1
cell surface receptor signaling pathway	1
adenylate cyclase-activating G protein-coupled receptor signaling pathway	1
positive regulation of cytosolic calcium ion concentration	1
positive regulation of gene expression	1
negative regulation of ossification	1
osteoclast differentiation	1
regulation of mRNA stability	1
positive regulation of calcium-mediated signaling	1
response to glucocorticoid	1
positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	1
positive regulation of ERK1 and ERK2 cascade	1
calcitonin family receptor signaling pathway	1
amylin receptor signaling pathway	1
positive regulation of cAMP/PKA signal transduction	1

Indications & clinical

Indications

4 indications (1 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
diabetes mellitus	4	MONDO:0005015	EFO:0000400
type 1 diabetes mellitus	3	MONDO:0005147	MONDO:0005147
type 2 diabetes mellitus	3	MONDO:0005148	MONDO:0005148
obesity disorder	2	MONDO:0011122	EFO:0001073

Clinical trials

Total trials: 24.

Phase distribution

Phase	Trials
PHASE4	7
Not specified	6
PHASE2	4
PHASE3	3
PHASE2/PHASE3	2
PHASE1/PHASE2	1
EARLY_PHASE1	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT00291772	PHASE4	COMPLETED	Continuous Subcutaneous Infusion of Pramlintide and Insulin
NCT00442767	PHASE4	COMPLETED	Post-meal Insulin Dosing With Adjuvant Pre-meal Pramlintide in Children With Type 1 Diabetes Mellitus
NCT00467649	PHASE4	COMPLETED	A Study to Characterize Regimens of Basal Insulin Intensified With Either Symlin® or Rapid Acting Insulin in Patients With Type 2 Diabetes
NCT00505882	PHASE4	WITHDRAWN	Efficacy of Pramlintide on Prevention of Weight Gain Early Onset of Type 1 Diabetes
NCT00690235	PHASE4	COMPLETED	Demonstrate the Effects of Pramlintide on Weight Reduction in Schizophrenia
NCT01269047	PHASE4	COMPLETED	Use of Exenatide and Pramlintide to Decrease Post-prandial Hyperglycemia
NCT01841359	PHASE4	COMPLETED	Pramlintide (Symlin) for the Treatment of Hypoglycemia Following Gastric Bypass Surgery
NCT00206258	PHASE3	COMPLETED	The Role of Amylin and Glucagon in T1DM
NCT00206297	PHASE3	COMPLETED	The Effect of Prolonged Pramlintide Infusion in Pediatric Diabetes
NCT01137695	PHASE3	UNKNOWN	Efficacy Study of High Dose Symlin to Treat Type 2 Diabetes Mellitus
NCT06046417	PHASE2/PHASE3	UNKNOWN	A Fully Automated Lyumjev and Pramlintide Delivery System for Adults With Type 1 Diabetes
NCT06619015	PHASE2/PHASE3	WITHDRAWN	Tailoring Obesity Treatment Trial
NCT00392925	PHASE2	COMPLETED	A Study to Evaluate the Effect on Body Weight of Leptin Administered in Conjunction With Pramlintide in Overweight and Obese Subjects
NCT00819234	PHASE2	COMPLETED	Extension Study of Protocol DFA102 to Examine the Long-Term Safety, Tolerability, and Effect on Body Weight of Pramlintide Administered in Combination With Metreleptin
NCT01165944	PHASE1/PHASE2	WITHDRAWN	Effectiveness Study of Pramlintide to Treat Post-Transplant Diabetes Mellitus
NCT01235741	PHASE2	TERMINATED	A Study To Examine The Efficacy And Safety Of Pramlintide+Metreleptin In Obese Subjects
NCT04074317	PHASE2	COMPLETED	Phase 2, Randomized, Open-Label, Crossover, PD/PK Study of a Novel Pram-Insulin Co-Formulation in Adults With T1D
NCT04252612	EARLY_PHASE1	WITHDRAWN	Biological Outcomes of Pramlintide in Resectable Cutaneous Squamous Cell Carcinoma: A Pilot Study
NCT00460304	Not specified	COMPLETED	The Effect of Pramlintide on Meal Time Insulin Bolus
NCT00489645	Not specified	COMPLETED	Effect of Hyperglycemia on Gastric Emptying Interactions With Pramlintide
NCT00691158	Not specified	UNKNOWN	A Study of the Functional Magnetic Resonance Imaging Response to Leptin and Pramlintide
NCT00842075	Not specified	COMPLETED	Pramlintide in Adolescents With Type 1 Diabetes
NCT05199714	Not specified	COMPLETED	A Fully-closed Loop, Pramlintide and Insulin, Artificial Pancreas Clinical Trial for Adults With Type 1 Diabetes
NCT06186063	Not specified	UNKNOWN	The Role of Amylin in Bone Metabolism

Clinical evidence (CIViC)

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

Pharmacology

Pharmacogenomics

No PharmGKB pharmacogenomic data curated for this drug.

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.

2 molecules share ≥1 primary target. Top 2 by shared-target count:

Molecule	Source	Status	Shared targets
CALCITONIN SALMON	ChEMBL	Phase 4 (approved)	CALCR
CAGRILINTIDE	ChEMBL	Phase 3	CALCR