SETMELANOTIDE

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C49H68N18O9S2
Molecular Weight	1117.3135
Optical Activity	UNSPECIFIED
Defined Stereocenters	8 / 8
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

C[C@H]1NC(=O)[C@H](CSSC[C@H](NC(=O)[C@H](CC2=CNC3=CC=CC=C23)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@@H](CC4=CC=CC=C4)NC(=O)[C@H](CC5=CN=CN5)NC1=O)C(N)=O)NC(=O)[C@H](CCCNC(N)=N)NC(C)=O

InChI

InChIKey=HDHDTKMUACZDAA-PHNIDTBTSA-N

InChI=1S/C49H68N18O9S2/c1-26-41(70)63-37(20-30-22-55-25-59-30)46(75)64-35(18-28-10-4-3-5-11-28)44(73)62-34(15-9-17-57-49(53)54)43(72)65-36(19-29-21-58-32-13-7-6-12-31(29)32)45(74)66-38(40(50)69)23-77-78-24-39(47(76)60-26)67-42(71)33(61-27(2)68)14-8-16-56-48(51)52/h3-7,10-13,21-22,25-26,33-39,58H,8-9,14-20,23-24H2,1-2H3,(H2,50,69)(H,55,59)(H,60,76)(H,61,68)(H,62,73)(H,63,70)(H,64,75)(H,65,72)(H,66,74)(H,67,71)(H4,51,52,56)(H4,53,54,57)/t26-,33+,34+,35-,36+,37+,38+,39+/m1/s1

HIDE SMILES / InChI

Molecular Formula	C49H68N18O9S2
Molecular Weight	1117.3135
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	8 / 8
E/Z Centers	1
Optical Activity	UNSPECIFIED

Description
Sources: https://www.imcivree.com|https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/213793s000lbl.pdf|https://pubmed.ncbi.nlm.nih.gov/33638809/

Setmelanotide (IMCIVREE™) is a melanocortin-4 (MC4) receptor agonist developed by Rhythm Pharmaceuticals (Rhythm) for the treatment of ultrarare genetic disorders of obesity. Setmelanotide was approved on 27 November 2020 in the USA as a subcutaneous (SC) injectable formulation for chronic weight management in adult and pediatric patients 6 years of age and older with obesity due to proopiomelanocortin (POMC), proprotein convertase subtilisin/kexin type 1 (PCSK1), or leptin receptor (LEPR) deficiency confirmed by genetic testing demonstrating variants in POMC, PCSK1, or LEPR genes that are interpreted as pathogenic, likely pathogenic, or of uncertain significance (VUS). Rhythm are also developing the drug for the treatment of obesity associated with other rare genetic disorders including Bardet–Biedl Syndrome, Alström Syndrome, POMC and other MC4R pathway heterozygous defciency obesities, and POMC epigenetic disorders.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Melanocortin receptor 4 8 Target ID: CHEMBL259 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/213793s000lbl.pdf	Agonist 2752		0.27 nM [EC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Obesity due to proopiomelanocortin (POMC), proprotein convertase subtilisin/kexin type 1 (PCSK1), or leptin receptor (LEPR) deficiency confirmed by genetic testing demonstrating variants in POMC, PCSK1, or LEPR genes that are interpreted as pathogenic, likely pathogenic, or of uncertain significance (VUS). 3 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/213793s000lbl.pdf	Primary		Approved 8583	IMCIVREE Approved Use Obesity due to proopiomelanocortin (POMC), proprotein convertase subtilisin/kexin type 1 (PCSK1), or leptin receptor (LEPR) deficiency confirmed by genetic testing demonstrating variants in POMC, PCSK1, or LEPR genes that are interpreted as pathogenic, likely pathogenic, or of uncertain significance (VUS). Launch Date 2020

C_max

Value	Dose	Analyte	Population
6.65 ng/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213793Orig1s000ClinPharmR.pdf#page=17 \| https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213793Orig1s000ClinPharmR.pdf#page=46	0.5 mg 1 times / day steady-state, subcutaneous dose: 0.5 mg route of administration: Subcutaneous experiment type: STEADY-STATE co-administered:	SETMELANOTIDE plasma	Homo sapiens population: UNHEALTHY age: UNKNOWN sex: FEMALE / MALE food status: UNKNOWN
10.4 ng/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213793Orig1s000ClinPharmR.pdf#page=17 \| https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213793Orig1s000ClinPharmR.pdf#page=46	1 mg 1 times / day steady-state, subcutaneous dose: 1 mg route of administration: Subcutaneous experiment type: STEADY-STATE co-administered:	SETMELANOTIDE plasma	Homo sapiens population: UNHEALTHY age: UNKNOWN sex: FEMALE / MALE food status: UNKNOWN
17.5 ng/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213793Orig1s000ClinPharmR.pdf#page=17 \| https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213793Orig1s000ClinPharmR.pdf#page=46	1.5 mg 1 times / day steady-state, subcutaneous dose: 1.5 mg route of administration: Subcutaneous experiment type: STEADY-STATE co-administered:	SETMELANOTIDE plasma	Homo sapiens population: UNHEALTHY age: UNKNOWN sex: FEMALE / MALE food status: UNKNOWN
25.1 ng/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213793Orig1s000ClinPharmR.pdf#page=17 \| https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213793Orig1s000ClinPharmR.pdf#page=46	2 mg 1 times / day steady-state, subcutaneous dose: 2 mg route of administration: Subcutaneous experiment type: STEADY-STATE co-administered:	SETMELANOTIDE plasma	Homo sapiens population: UNHEALTHY age: UNKNOWN sex: FEMALE / MALE food status: UNKNOWN
32.8 ng/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213793Orig1s000ClinPharmR.pdf#page=17 \| https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213793Orig1s000ClinPharmR.pdf#page=46	2.5 mg 1 times / day steady-state, subcutaneous dose: 2.5 mg route of administration: Subcutaneous experiment type: STEADY-STATE co-administered:	SETMELANOTIDE plasma	Homo sapiens population: UNHEALTHY age: UNKNOWN sex: FEMALE / MALE food status: UNKNOWN
38 ng/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213793Orig1s000ClinPharmR.pdf#page=17 \| https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213793Orig1s000ClinPharmR.pdf#page=46	2.5 mg 1 times / day steady-state, subcutaneous dose: 2.5 mg route of administration: Subcutaneous experiment type: STEADY-STATE co-administered:	SETMELANOTIDE plasma	Homo sapiens population: UNHEALTHY age: UNKNOWN sex: FEMALE / MALE food status: UNKNOWN
25.4 ng/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213793Orig1s000ClinPharmR.pdf#page=34	0.0215 mg/kg single, subcutaneous dose: 0.0215 mg/kg route of administration: Subcutaneous experiment type: SINGLE co-administered:	SETMELANOTIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
14.2 ng/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213793Orig1s000ClinPharmR.pdf#page=38	0.75 mg 2 times / day steady-state, subcutaneous dose: 0.75 mg route of administration: Subcutaneous experiment type: STEADY-STATE co-administered:	SETMELANOTIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
23 ng/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213793Orig1s000ClinPharmR.pdf#page=38	1.5 mg 1 times / day steady-state, subcutaneous dose: 1.5 mg route of administration: Subcutaneous experiment type: STEADY-STATE co-administered:	SETMELANOTIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
27.5 ng/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213793Orig1s000ClinPharmR.pdf#page=38	2 mg 1 times / day steady-state, subcutaneous dose: 2 mg route of administration: Subcutaneous experiment type: STEADY-STATE co-administered:	SETMELANOTIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
19.7 ng/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213793Orig1s000ClinPharmR.pdf#page=40	2 mg single, subcutaneous dose: 2 mg route of administration: Subcutaneous experiment type: SINGLE co-administered:	SETMELANOTIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
24.8 ng/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213793Orig1s000ClinPharmR.pdf#page=43	1.5 mg single, subcutaneous dose: 1.5 mg route of administration: Subcutaneous experiment type: SINGLE co-administered:	SETMELANOTIDE plasma	Homo sapiens population: UNHEALTHY age: UNKNOWN sex: FEMALE / MALE food status: UNKNOWN
17.5 ng/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213793Orig1s000ClinPharmR.pdf#page=43	2 mg single, subcutaneous dose: 2 mg route of administration: Subcutaneous experiment type: SINGLE co-administered:	SETMELANOTIDE plasma	Homo sapiens population: UNHEALTHY age: UNKNOWN sex: FEMALE / MALE food status: UNKNOWN
6.47 ng/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213793Orig1s000ClinPharmR.pdf#page=52	0.5 mg 1 times / day unknown, subcutaneous dose: 0.5 mg route of administration: Subcutaneous experiment type: UNKNOWN co-administered:	SETMELANOTIDE plasma	Homo sapiens population: UNHEALTHY age: UNKNOWN sex: FEMALE / MALE food status: UNKNOWN
11.5 ng/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213793Orig1s000ClinPharmR.pdf#page=52	1 mg 1 times / day unknown, subcutaneous dose: 1 mg route of administration: Subcutaneous experiment type: UNKNOWN co-administered:	SETMELANOTIDE plasma	Homo sapiens population: UNHEALTHY age: UNKNOWN sex: FEMALE / MALE food status: UNKNOWN
22.4 ng/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213793Orig1s000ClinPharmR.pdf#page=52	1.5 mg 1 times / day unknown, subcutaneous dose: 1.5 mg route of administration: Subcutaneous experiment type: UNKNOWN co-administered:	SETMELANOTIDE plasma	Homo sapiens population: UNHEALTHY age: UNKNOWN sex: FEMALE / MALE food status: UNKNOWN
24.5 ng/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213793Orig1s000ClinPharmR.pdf#page=52	2 mg 1 times / day unknown, subcutaneous dose: 2 mg route of administration: Subcutaneous experiment type: UNKNOWN co-administered:	SETMELANOTIDE plasma	Homo sapiens population: UNHEALTHY age: UNKNOWN sex: FEMALE / MALE food status: UNKNOWN
24.4 ng/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213793Orig1s000ClinPharmR.pdf#page=52	2.5 mg 1 times / day unknown, subcutaneous dose: 2.5 mg route of administration: Subcutaneous experiment type: UNKNOWN co-administered:	SETMELANOTIDE plasma	Homo sapiens population: UNHEALTHY age: UNKNOWN sex: FEMALE / MALE food status: UNKNOWN
7.21 ng/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213793Orig1s000ClinPharmR.pdf#page=61	0.5 mg 1 times / day unknown, subcutaneous dose: 0.5 mg route of administration: Subcutaneous experiment type: UNKNOWN co-administered:	SETMELANOTIDE plasma	Homo sapiens population: UNHEALTHY age: UNKNOWN sex: FEMALE / MALE food status: UNKNOWN
10.4 ng/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213793Orig1s000ClinPharmR.pdf#page=61	1 mg 1 times / day unknown, subcutaneous dose: 1 mg route of administration: Subcutaneous experiment type: UNKNOWN co-administered:	SETMELANOTIDE plasma	Homo sapiens population: UNHEALTHY age: UNKNOWN sex: FEMALE / MALE food status: UNKNOWN
17 ng/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213793Orig1s000ClinPharmR.pdf#page=61	1.5 mg 1 times / day unknown, subcutaneous dose: 1.5 mg route of administration: Subcutaneous experiment type: UNKNOWN co-administered:	SETMELANOTIDE plasma	Homo sapiens population: UNHEALTHY age: UNKNOWN sex: FEMALE / MALE food status: UNKNOWN
23.9 ng/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213793Orig1s000ClinPharmR.pdf#page=61	2 mg 1 times / day unknown, subcutaneous dose: 2 mg route of administration: Subcutaneous experiment type: UNKNOWN co-administered:	SETMELANOTIDE plasma	Homo sapiens population: UNHEALTHY age: UNKNOWN sex: FEMALE / MALE food status: UNKNOWN
31.1 ng/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213793Orig1s000ClinPharmR.pdf#page=61	2.5 mg 1 times / day unknown, subcutaneous dose: 2.5 mg route of administration: Subcutaneous experiment type: UNKNOWN co-administered:	SETMELANOTIDE plasma	Homo sapiens population: UNHEALTHY age: UNKNOWN sex: FEMALE / MALE food status: UNKNOWN
38.9 ng/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213793Orig1s000ClinPharmR.pdf#page=61	3 mg 1 times / day unknown, subcutaneous dose: 3 mg route of administration: Subcutaneous experiment type: UNKNOWN co-administered:	SETMELANOTIDE plasma	Homo sapiens population: UNHEALTHY age: UNKNOWN sex: FEMALE / MALE food status: UNKNOWN

AUC

Value	Dose	Analyte	Population
35.8 ng × h/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213793Orig1s000ClinPharmR.pdf#page=17 \| https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213793Orig1s000ClinPharmR.pdf#page=46	0.5 mg 1 times / day steady-state, subcutaneous dose: 0.5 mg route of administration: Subcutaneous experiment type: STEADY-STATE co-administered:	SETMELANOTIDE plasma	Homo sapiens population: UNHEALTHY age: UNKNOWN sex: FEMALE / MALE food status: UNKNOWN
59.3 ng × h/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213793Orig1s000ClinPharmR.pdf#page=17 \| https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213793Orig1s000ClinPharmR.pdf#page=46	1 mg 1 times / day steady-state, subcutaneous dose: 1 mg route of administration: Subcutaneous experiment type: STEADY-STATE co-administered:	SETMELANOTIDE plasma	Homo sapiens population: UNHEALTHY age: UNKNOWN sex: FEMALE / MALE food status: UNKNOWN
106 ng × h/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213793Orig1s000ClinPharmR.pdf#page=17 \| https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213793Orig1s000ClinPharmR.pdf#page=46	1.5 mg 1 times / day steady-state, subcutaneous dose: 1.5 mg route of administration: Subcutaneous experiment type: STEADY-STATE co-administered:	SETMELANOTIDE plasma	Homo sapiens population: UNHEALTHY age: UNKNOWN sex: FEMALE / MALE food status: UNKNOWN
146 ng × h/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213793Orig1s000ClinPharmR.pdf#page=17 \| https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213793Orig1s000ClinPharmR.pdf#page=46	2 mg 1 times / day steady-state, subcutaneous dose: 2 mg route of administration: Subcutaneous experiment type: STEADY-STATE co-administered:	SETMELANOTIDE plasma	Homo sapiens population: UNHEALTHY age: UNKNOWN sex: FEMALE / MALE food status: UNKNOWN
188 ng × h/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213793Orig1s000ClinPharmR.pdf#page=17 \| https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213793Orig1s000ClinPharmR.pdf#page=46	2.5 mg 1 times / day steady-state, subcutaneous dose: 2.5 mg route of administration: Subcutaneous experiment type: STEADY-STATE co-administered:	SETMELANOTIDE plasma	Homo sapiens population: UNHEALTHY age: UNKNOWN sex: FEMALE / MALE food status: UNKNOWN
207 ng × h/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213793Orig1s000ClinPharmR.pdf#page=17 \| https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213793Orig1s000ClinPharmR.pdf#page=46	2.5 mg 1 times / day steady-state, subcutaneous dose: 2.5 mg route of administration: Subcutaneous experiment type: STEADY-STATE co-administered:	SETMELANOTIDE plasma	Homo sapiens population: UNHEALTHY age: UNKNOWN sex: FEMALE / MALE food status: UNKNOWN
243 ng × h/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213793Orig1s000ClinPharmR.pdf#page=38	0.75 mg 2 times / day steady-state, subcutaneous dose: 0.75 mg route of administration: Subcutaneous experiment type: STEADY-STATE co-administered:	SETMELANOTIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
271 ng × h/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213793Orig1s000ClinPharmR.pdf#page=38	1.5 mg 1 times / day steady-state, subcutaneous dose: 1.5 mg route of administration: Subcutaneous experiment type: STEADY-STATE co-administered:	SETMELANOTIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
347 ng × h/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213793Orig1s000ClinPharmR.pdf#page=38	2 mg 1 times / day steady-state, subcutaneous dose: 2 mg route of administration: Subcutaneous experiment type: STEADY-STATE co-administered:	SETMELANOTIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
253 ng × h/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213793Orig1s000ClinPharmR.pdf#page=40	2 mg single, subcutaneous dose: 2 mg route of administration: Subcutaneous experiment type: SINGLE co-administered:	SETMELANOTIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
111 ng × h/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213793Orig1s000ClinPharmR.pdf#page=43	1.5 mg single, subcutaneous dose: 1.5 mg route of administration: Subcutaneous experiment type: SINGLE co-administered:	SETMELANOTIDE plasma	Homo sapiens population: UNHEALTHY age: UNKNOWN sex: FEMALE / MALE food status: UNKNOWN
36.2 ng × h/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213793Orig1s000ClinPharmR.pdf#page=43	2 mg single, subcutaneous dose: 2 mg route of administration: Subcutaneous experiment type: SINGLE co-administered:	SETMELANOTIDE plasma	Homo sapiens population: UNHEALTHY age: UNKNOWN sex: FEMALE / MALE food status: UNKNOWN
38.3 ng × h/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213793Orig1s000ClinPharmR.pdf#page=52	0.5 mg 1 times / day unknown, subcutaneous dose: 0.5 mg route of administration: Subcutaneous experiment type: UNKNOWN co-administered:	SETMELANOTIDE plasma	Homo sapiens population: UNHEALTHY age: UNKNOWN sex: FEMALE / MALE food status: UNKNOWN
74.2 ng × h/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213793Orig1s000ClinPharmR.pdf#page=52	1 mg 1 times / day unknown, subcutaneous dose: 1 mg route of administration: Subcutaneous experiment type: UNKNOWN co-administered:	SETMELANOTIDE plasma	Homo sapiens population: UNHEALTHY age: UNKNOWN sex: FEMALE / MALE food status: UNKNOWN
147 ng × h/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213793Orig1s000ClinPharmR.pdf#page=52	1.5 mg 1 times / day unknown, subcutaneous dose: 1.5 mg route of administration: Subcutaneous experiment type: UNKNOWN co-administered:	SETMELANOTIDE plasma	Homo sapiens population: UNHEALTHY age: UNKNOWN sex: FEMALE / MALE food status: UNKNOWN
159 ng × h/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213793Orig1s000ClinPharmR.pdf#page=52	2 mg 1 times / day unknown, subcutaneous dose: 2 mg route of administration: Subcutaneous experiment type: UNKNOWN co-administered:	SETMELANOTIDE plasma	Homo sapiens population: UNHEALTHY age: UNKNOWN sex: FEMALE / MALE food status: UNKNOWN
180 ng × h/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213793Orig1s000ClinPharmR.pdf#page=52	2.5 mg 1 times / day unknown, subcutaneous dose: 2.5 mg route of administration: Subcutaneous experiment type: UNKNOWN co-administered:	SETMELANOTIDE plasma	Homo sapiens population: UNHEALTHY age: UNKNOWN sex: FEMALE / MALE food status: UNKNOWN
56.2 ng × h/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213793Orig1s000ClinPharmR.pdf#page=61	0.5 mg 1 times / day unknown, subcutaneous dose: 0.5 mg route of administration: Subcutaneous experiment type: UNKNOWN co-administered:	SETMELANOTIDE plasma	Homo sapiens population: UNHEALTHY age: UNKNOWN sex: FEMALE / MALE food status: UNKNOWN
79.1 ng × h/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213793Orig1s000ClinPharmR.pdf#page=61	1 mg 1 times / day unknown, subcutaneous dose: 1 mg route of administration: Subcutaneous experiment type: UNKNOWN co-administered:	SETMELANOTIDE plasma	Homo sapiens population: UNHEALTHY age: UNKNOWN sex: FEMALE / MALE food status: UNKNOWN
130 ng × h/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213793Orig1s000ClinPharmR.pdf#page=61	1.5 mg 1 times / day unknown, subcutaneous dose: 1.5 mg route of administration: Subcutaneous experiment type: UNKNOWN co-administered:	SETMELANOTIDE plasma	Homo sapiens population: UNHEALTHY age: UNKNOWN sex: FEMALE / MALE food status: UNKNOWN
178 ng × h/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213793Orig1s000ClinPharmR.pdf#page=61	2 mg 1 times / day unknown, subcutaneous dose: 2 mg route of administration: Subcutaneous experiment type: UNKNOWN co-administered:	SETMELANOTIDE plasma	Homo sapiens population: UNHEALTHY age: UNKNOWN sex: FEMALE / MALE food status: UNKNOWN
260 ng × h/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213793Orig1s000ClinPharmR.pdf#page=61	2.5 mg 1 times / day unknown, subcutaneous dose: 2.5 mg route of administration: Subcutaneous experiment type: UNKNOWN co-administered:	SETMELANOTIDE plasma	Homo sapiens population: UNHEALTHY age: UNKNOWN sex: FEMALE / MALE food status: UNKNOWN
383 ng × h/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213793Orig1s000ClinPharmR.pdf#page=61	3 mg 1 times / day unknown, subcutaneous dose: 3 mg route of administration: Subcutaneous experiment type: UNKNOWN co-administered:	SETMELANOTIDE plasma	Homo sapiens population: UNHEALTHY age: UNKNOWN sex: FEMALE / MALE food status: UNKNOWN

T_1/2

Value	Dose	Analyte	Population
8.98 h OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213793Orig1s000ClinPharmR.pdf#page=34	0.0215 mg/kg single, subcutaneous dose: 0.0215 mg/kg route of administration: Subcutaneous experiment type: SINGLE co-administered:	SETMELANOTIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
5.91 h OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213793Orig1s000ClinPharmR.pdf#page=38	0.75 mg 2 times / day steady-state, subcutaneous dose: 0.75 mg route of administration: Subcutaneous experiment type: STEADY-STATE co-administered:	SETMELANOTIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
7.55 h OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213793Orig1s000ClinPharmR.pdf#page=38	1.5 mg 1 times / day steady-state, subcutaneous dose: 1.5 mg route of administration: Subcutaneous experiment type: STEADY-STATE co-administered:	SETMELANOTIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
7.73 h OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213793Orig1s000ClinPharmR.pdf#page=38	2 mg 1 times / day steady-state, subcutaneous dose: 2 mg route of administration: Subcutaneous experiment type: STEADY-STATE co-administered:	SETMELANOTIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
6.18 h OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213793Orig1s000ClinPharmR.pdf#page=40	2 mg single, subcutaneous dose: 2 mg route of administration: Subcutaneous experiment type: SINGLE co-administered:	SETMELANOTIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

F_unbound

Value	Dose	Co-administered	Analyte	Population
20.9% OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213793Orig1s000PharmR.pdf#page=27			SETMELANOTIDE plasma	Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN

Doses

Dose	Population	Adverse events
3 mg 1 times / day multiple, subcutaneous Highest studied dose Dose: 3 mg, 1 times / day Route: subcutaneous Route: multiple Dose: 3 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213793Orig1s000MedR.pdf#page=147	unhealthy, CHILD\|ADOLESCENT\|ADULT Health Status: unhealthy Age Group: CHILD\|ADOLESCENT\|ADULT Sex: M+F Food Status: UNKNOWN Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213793Orig1s000MedR.pdf#page=147	Disc. AE: Depression, Upper respiratory tract infection... Other AEs: Spontaneous penile erection, Suicidal ideation... AEs leading to discontinuation/dose reduction: Depression (4, 29.6%) Upper respiratory tract infection (25.9%) Asthenia (18.5%) Injection site reaction (4, 14.8%) Eosinophilia Other AEs: Spontaneous penile erection (23.1%) Suicidal ideation (grade 5, 11.1%) Pneumonia Adrenal insufficiency Panic attack (1) Hyperhidrosis Pleuritis Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213793Orig1s000MedR.pdf#page=147

AEs

AE	Significance	Dose	Population
Adrenal insufficiency		3 mg 1 times / day multiple, subcutaneous Highest studied dose Dose: 3 mg, 1 times / day Route: subcutaneous Route: multiple Dose: 3 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213793Orig1s000MedR.pdf#page=147	unhealthy, CHILD\|ADOLESCENT\|ADULT Health Status: unhealthy Age Group: CHILD\|ADOLESCENT\|ADULT Sex: M+F Food Status: UNKNOWN Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213793Orig1s000MedR.pdf#page=147
Hyperhidrosis		3 mg 1 times / day multiple, subcutaneous Highest studied dose Dose: 3 mg, 1 times / day Route: subcutaneous Route: multiple Dose: 3 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213793Orig1s000MedR.pdf#page=147	unhealthy, CHILD\|ADOLESCENT\|ADULT Health Status: unhealthy Age Group: CHILD\|ADOLESCENT\|ADULT Sex: M+F Food Status: UNKNOWN Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213793Orig1s000MedR.pdf#page=147
Pleuritis		3 mg 1 times / day multiple, subcutaneous Highest studied dose Dose: 3 mg, 1 times / day Route: subcutaneous Route: multiple Dose: 3 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213793Orig1s000MedR.pdf#page=147	unhealthy, CHILD\|ADOLESCENT\|ADULT Health Status: unhealthy Age Group: CHILD\|ADOLESCENT\|ADULT Sex: M+F Food Status: UNKNOWN Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213793Orig1s000MedR.pdf#page=147
Pneumonia		3 mg 1 times / day multiple, subcutaneous Highest studied dose Dose: 3 mg, 1 times / day Route: subcutaneous Route: multiple Dose: 3 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213793Orig1s000MedR.pdf#page=147	unhealthy, CHILD\|ADOLESCENT\|ADULT Health Status: unhealthy Age Group: CHILD\|ADOLESCENT\|ADULT Sex: M+F Food Status: UNKNOWN Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213793Orig1s000MedR.pdf#page=147
Panic attack	1	3 mg 1 times / day multiple, subcutaneous Highest studied dose Dose: 3 mg, 1 times / day Route: subcutaneous Route: multiple Dose: 3 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213793Orig1s000MedR.pdf#page=147	unhealthy, CHILD\|ADOLESCENT\|ADULT Health Status: unhealthy Age Group: CHILD\|ADOLESCENT\|ADULT Sex: M+F Food Status: UNKNOWN Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213793Orig1s000MedR.pdf#page=147
Asthenia	18.5% Disc. AE	3 mg 1 times / day multiple, subcutaneous Highest studied dose Dose: 3 mg, 1 times / day Route: subcutaneous Route: multiple Dose: 3 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213793Orig1s000MedR.pdf#page=147	unhealthy, CHILD\|ADOLESCENT\|ADULT Health Status: unhealthy Age Group: CHILD\|ADOLESCENT\|ADULT Sex: M+F Food Status: UNKNOWN Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213793Orig1s000MedR.pdf#page=147
Spontaneous penile erection	23.1%	3 mg 1 times / day multiple, subcutaneous Highest studied dose Dose: 3 mg, 1 times / day Route: subcutaneous Route: multiple Dose: 3 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213793Orig1s000MedR.pdf#page=147	unhealthy, CHILD\|ADOLESCENT\|ADULT Health Status: unhealthy Age Group: CHILD\|ADOLESCENT\|ADULT Sex: M+F Food Status: UNKNOWN Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213793Orig1s000MedR.pdf#page=147
Upper respiratory tract infection	25.9% Disc. AE	3 mg 1 times / day multiple, subcutaneous Highest studied dose Dose: 3 mg, 1 times / day Route: subcutaneous Route: multiple Dose: 3 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213793Orig1s000MedR.pdf#page=147	unhealthy, CHILD\|ADOLESCENT\|ADULT Health Status: unhealthy Age Group: CHILD\|ADOLESCENT\|ADULT Sex: M+F Food Status: UNKNOWN Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213793Orig1s000MedR.pdf#page=147
Injection site reaction	4, 14.8% Disc. AE	3 mg 1 times / day multiple, subcutaneous Highest studied dose Dose: 3 mg, 1 times / day Route: subcutaneous Route: multiple Dose: 3 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213793Orig1s000MedR.pdf#page=147	unhealthy, CHILD\|ADOLESCENT\|ADULT Health Status: unhealthy Age Group: CHILD\|ADOLESCENT\|ADULT Sex: M+F Food Status: UNKNOWN Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213793Orig1s000MedR.pdf#page=147
Depression	4, 29.6% Disc. AE	3 mg 1 times / day multiple, subcutaneous Highest studied dose Dose: 3 mg, 1 times / day Route: subcutaneous Route: multiple Dose: 3 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213793Orig1s000MedR.pdf#page=147	unhealthy, CHILD\|ADOLESCENT\|ADULT Health Status: unhealthy Age Group: CHILD\|ADOLESCENT\|ADULT Sex: M+F Food Status: UNKNOWN Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213793Orig1s000MedR.pdf#page=147
Eosinophilia	Disc. AE	3 mg 1 times / day multiple, subcutaneous Highest studied dose Dose: 3 mg, 1 times / day Route: subcutaneous Route: multiple Dose: 3 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213793Orig1s000MedR.pdf#page=147	unhealthy, CHILD\|ADOLESCENT\|ADULT Health Status: unhealthy Age Group: CHILD\|ADOLESCENT\|ADULT Sex: M+F Food Status: UNKNOWN Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213793Orig1s000MedR.pdf#page=147
Suicidal ideation	grade 5, 11.1%	3 mg 1 times / day multiple, subcutaneous Highest studied dose Dose: 3 mg, 1 times / day Route: subcutaneous Route: multiple Dose: 3 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213793Orig1s000MedR.pdf#page=147	unhealthy, CHILD\|ADOLESCENT\|ADULT Health Status: unhealthy Age Group: CHILD\|ADOLESCENT\|ADULT Sex: M+F Food Status: UNKNOWN Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213793Orig1s000MedR.pdf#page=147

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inducer 1087 inhibitor 2252	inhibitor 2438	inhibitor 2507	inhibitor 2217

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
OATP1B1 1079 OATP1B3 961 CYP2C19 2057 CYP1A2 2153 CYP2B6 926 CYP2A6 879 CYP2C8 1057 P-gp 1741 BCRP 910 OCT2 779 OAT1 725 MATE1 415 OAT3 747 MATE2K 17	OCT2 434 OATP1B3 435 OATP1B1 503 MATE1 182 P-gp 2052 OAT1 395 MATE2K 6 BCRP 697 OAT3 391	CYP1A2 832 CYP2B6 669

Drug as perpetrator

Target	Modality	Activity
CYP1A2 2333	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213793Orig1s000PharmR.pdf#page=28 Page: 28.0	no [IC50 >1000 uM]
CYP2C19 2141	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213793Orig1s000PharmR.pdf#page=28 Page: 28.0	no [IC50 >1000 uM]
CYP2C9 2497	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213793Orig1s000PharmR.pdf#page=28 Page: 28.0	no [IC50 >1000 uM]
CYP2D6 2546	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213793Orig1s000PharmR.pdf#page=28 Page: 28.0	no [IC50 >1000 uM]
BCRP 985	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213793Orig1s000ClinPharmR.pdf#page=26 Page: 26.0	no
CYP1A2 2333	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213793Orig1s000ClinPharmR.pdf#page=26 Page: 26.0	no
CYP2A6 911	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213793Orig1s000ClinPharmR.pdf#page=25 Page: 25.0	no
CYP2B6 1160	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213793Orig1s000ClinPharmR.pdf#page=26 Page: 26.0	no
CYP2B6 1160	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213793Orig1s000ClinPharmR.pdf#page=25 Page: 25.0	no
CYP2C8 1117	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213793Orig1s000ClinPharmR.pdf#page=25 Page: 25.0	no
CYP3A4 2633	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213793Orig1s000ClinPharmR.pdf#page=26 Page: 26.0	no
MATE1 416	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213793Orig1s000ClinPharmR.pdf#page=26 Page: 26.0	no
MATE2K 17	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213793Orig1s000ClinPharmR.pdf#page=26 Page: 26.0	no
OAT1 730	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213793Orig1s000ClinPharmR.pdf#page=26 Page: 26.0	no
OAT3 749	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213793Orig1s000ClinPharmR.pdf#page=26 Page: 26.0	no
OATP1B1 1095	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213793Orig1s000ClinPharmR.pdf#page=26 Page: 26.0	no
OATP1B3 970	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213793Orig1s000ClinPharmR.pdf#page=26 Page: 26.0	no
OCT2 782	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213793Orig1s000ClinPharmR.pdf#page=26 Page: 26.0	no
P-gp 1932	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213793Orig1s000ClinPharmR.pdf#page=26 Page: 26.0	no
CYP3A4 2633	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213793Orig1s000PharmR.pdf#page=28 Page: 28.0	week [IC50 54.1 uM]

Drug as victim

Target	Modality	Activity
BCRP 697	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213793Orig1s000ClinPharmR.pdf#page=26 Page: 26.0	no
MATE1 182	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213793Orig1s000ClinPharmR.pdf#page=26 Page: 26.0	no
MATE2K 6	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213793Orig1s000ClinPharmR.pdf#page=26 Page: 26.0	no
OAT1 395	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213793Orig1s000ClinPharmR.pdf#page=26 Page: 26.0	no
OAT3 391	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213793Orig1s000ClinPharmR.pdf#page=26 Page: 26.0	no
OATP1B1 503	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213793Orig1s000ClinPharmR.pdf#page=26 Page: 26.0	no
OATP1B3 435	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213793Orig1s000ClinPharmR.pdf#page=26 Page: 26.0	no
OCT2 434	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213793Orig1s000ClinPharmR.pdf#page=26 Page: 26.0	no
P-gp 2052	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213793Orig1s000ClinPharmR.pdf#page=26 Page: 26.0	no

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 2263	inhibitor 2237 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213793Orig1s000PharmR.pdf#page=25 Page: 25.0

PubMed

Title	Date	PubMed

Sample Use Guides

In Vivo Use Guide

Obesity due to deficiency of POMC, PCSK1, or LEPR: 2 mg (0.2 mL) injected subcutaneously once daily for 2 weeks.

Route of Administration: Other

In Vitro Use Guide

Setmelanotide (RM-493) binds human MC4R with Ki value of 0.71 nM in radioligand binding assay and activated MC4R with EC50 value of 1.5 nM in intracellular cAMP production assay.

Substance Class	Chemical Created by `admin` on `Mon Mar 31 22:05:41 GMT 2025` Edited by `admin` on `Mon Mar 31 22:05:41 GMT 2025`
Record UNII	N7T15V1FUY
Record Status	`FAILED`
Record Version

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Name

Type

Language

SETMELANOTIDE

Official Name

English

setmelanotide [INN]

Preferred Name

English

L-CYSTEINAMIDE, N2-ACETYL-L-ARGINYL-L-CYSTEINYL-D-ALANYL-L-HISTIDYL-D-PHENYLALANYL-L-ARGINYL-L-TRYPTOPHYL-, CYCLIC (2->8)-DISULFIDE

Systematic Name

English

Setmelanotide [WHO-DD]

Common Name

English

BIM-22493

Code

English

SETMELANOTIDE [USAN]

Common Name

English

RM-493

Code

English

Classification Tree Code System Code

FDA ORPHAN DRUG

700719