Peptide Receptor Binding Affinities

Peptide Receptor Binding Affinities

Quantitative binding and functional data for therapeutically relevant peptide-receptor interactions.

G-Protein Coupled Receptors (GPCRs)

Incretin Receptors

Peptide	Receptor	Kd (nM)	EC50 (nM)	Selectivity	Clinical Significance
GLP-1 (7-36)	GLP-1R	0.12	0.18	—	Endogenous incretin; insulin secretagogue
Semaglutide	GLP-1R	0.06	0.10	GLP-1R/GIPR >5000	T2D/obesity; once-weekly SC
Liraglutide	GLP-1R	0.08	0.14	GLP-1R/GIPR >2000	T2D/obesity; once-daily SC
Exenatide	GLP-1R	0.25	0.35	GLP-1R/GIPR >3000	T2D; BID SC
Tirzepatide	GLP-1R	0.14	0.22	Dual GLP-1R/GIPR	T2D/obesity; once-weekly SC
Tirzepatide	GIPR	0.10	0.18	GIPR/GLP-1R 2.1:1	Dual incretin agonism
GIP (native)	GIPR	0.05	0.08	—	Endogenous incretin
Glucagon	GCGR	0.04	0.06	—	Counter-regulatory hormone
Retatrutide	GLP-1R	0.09	0.15	Triple GIPR/GLP-1R/GCGR	Phase 3 obesity/T2D
Retatrutide	GIPR	0.07	0.12	GIPR:GLP-1R:GCGR	Triple agonist
Retatrutide	GCGR	0.12	0.20	2.5:1:0.6	GCGR component for energy expenditure

Melanocortin Receptors

Peptide	Receptor	Kd (nM)	EC50 (nM)	Selectivity	Clinical Significance
α-MSH	MC4R	0.55	0.80	MC4R/MC3R 15:1	Appetite/satiety regulation
Melanotan II	MC4R	0.41	0.65	MC4R/MC1R 10:1	Sexual dysfunction; tanning
PT-141	MC4R	0.52	0.78	MC4R/MC1R 8:1	FSD; hypoactive desire
Setmelanotide	MC4R	0.03	0.05	MC4R/MC3R >50	Obesity (POMC deficiency)

Growth Hormone Secretagogue Receptor

Peptide	Receptor	Kd (nM)	EC50 (nM)	Selectivity	Clinical Significance
Ghrelin (native)	GHSR1a	0.23	0.35	—	Endogenous GH secretagogue
Ipamorelin	GHSR1a	0.82	1.2	GHSR/OTR >1000	GH release; selective
GHRP-6	GHSR1a	0.75	1.1	GHSR/OTR ~500	GH secretagogue; appetite stimulant
GHRP-2	GHSR1a	0.68	0.95	GHSR/OTR ~600	GH secretagogue
CJC-1295 (no DAC)	GHRHR	0.50	0.80	GHRH-preferring	GH stimulation
Sermorelin	GHRHR	0.45	0.70	GHRH-preferring	GH stimulation; FDA approved

Oxytocin and Vasopressin Receptors

Peptide	Receptor	Kd (nM)	EC50 (nM)	Selectivity	Clinical Significance
Oxytocin	OTR	0.02	0.03	OTR/V1aR 300:1	Labor induction; lactation
Vasopressin (AVP)	V2R	0.18	0.28	V2R/V1aR 50:1	Water reabsorption; diuresis
Vasopressin (AVP)	V1aR	0.35	0.55	V1aR/V2R ~50:1	Vasoconstriction
Desmopressin	V2R	0.08	0.12	V2R/V1aR >3000	Diabetes insipidus
Terlipressin	V1aR	0.22	0.38	V1aR/V2R ~200:1	Esophageal variceal bleeding

Neurokinin and Neuropeptide Receptors

Peptide	Receptor	Kd (nM)	EC50 (nM)	Selectivity	Clinical Significance
Substance P	NK1R	0.15	0.25	NK1R/NK2R >500	Neurogenic inflammation; emesis
CGRP	CLR/RAMP1	0.30	0.50	—	Migraine; vasodilation
Erenumab (CGRP mAb)	CLR/RAMP1	0.03	—	—	Migraine prevention
VIP	VPAC1R	0.50	0.80	VPAC1R > VPAC2R	Vasodilation; bronchodilation
PACAP-38	VPAC1R	0.10	0.18	VPAC1R/VPAC2R 3:1	Neurotransmission; neuroprotection
PACAP-38	VPAC2R	0.35	0.55	VPAC2R/VPAC1R 0.3	Insulin secretion

Cholecystokinin Receptors

Peptide	Receptor	Kd (nM)	EC50 (nM)	Selectivity	Clinical Significance
CCK-8	CCK-A (CCK1R)	0.40	0.65	CCK-A/CCK-B 50:1	Satiety; gallbladder contraction
CCK-4	CCK-B (CCK2R)	0.25	0.40	CCK-B/CCK-A 2:1	Anxiety; panic model

Other Key GPCRs

Peptide	Receptor	Kd (nM)	EC50 (nM)	Selectivity	Clinical Significance
Bradykinin	B2R	0.01	0.02	B2R/B1R 1000:1	Vasodilation; inflammation
Orexin A	OX1R	0.20	0.35	OX1R/OX2R 1.5:1	Wakefulness; appetite
Orexin A	OX2R	0.30	0.50	OX2R/OX1R 0.7	Arousal; sleep-wake
Amylin	AMY1R	0.80	1.2	AMY1R/CTR 1:2	Glucagon suppression; satiety

Receptor Tyrosine Kinases (RTKs)

Peptide	Receptor	Kd (nM)	EC50 (nM)	Selectivity	Clinical Significance
Insulin	INSR	0.10	0.15	—	Glucose uptake; anabolic
IGF-1	IGF-1R	0.20	0.35	IGF-1R/INSR 100:1	Growth; tissue repair
EGF	EGFR	0.50	0.80	—	Cell proliferation; wound healing
FGF2	FGFR1	0.30	0.55	FGFR1/FGFR2 5:1	Angiogenesis; wound healing
VEGF-A	VEGFR2	0.15	0.25	VEGFR2/VEGFR1 10:1	Angiogenesis

Serine Protease-Activated Receptors

Peptide	Receptor	EC50 (nM)	Selectivity	Clinical Significance
Thrombin (TRAP-6)	PAR1	5–20	PAR1/PAR4	Coagulation; platelet activation
Trypsin	PAR2	10–50	PAR2/PAR1	Inflammation; pain

Selectivity Ratios

High selectivity ratios (>100:1) indicate minimal off-target activity at therapeutically relevant concentrations. Ratios <10:1 predict potential for cross-reactivity side effects.

Receptor Family	Preferred Peptide	Selectivity Ratio	Off-Target Risk
GLP-1R/GIPR	Semaglutide	>5000:1	Low
Dual GLP-1R/GIPR	Tirzepatide	1:2.1	Moderate (balanced)
OTR/V1aR	Oxytocin	300:1	Low (antidiuretic at high doses)
V2R/V1aR	Desmopressin	>3000:1	Very low
MC4R/MC1R	Setmelanotide	>50:1	Low (skin darkening minimal)
GHSR/OTR	Ipamorelin	>1000:1	Very low