MACIMORELIN

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C26H30N6O3
Molecular Weight	474.5558
Optical Activity	UNSPECIFIED
Defined Stereocenters	2 / 2
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CC(C)(C(=N[C@]([H])(Cc1c[nH]c2ccccc12)C(=N[C@]([H])(Cc3c[nH]c4ccccc34)N=CO)O)O)N

InChI

InChIKey=UJVDJAPJQWZRFR-DHIUTWEWSA-N

InChI=1S/C26H30N6O3/c1-26(2,27)25(35)31-22(11-16-13-28-20-9-5-3-7-18(16)20)24(34)32-23(30-15-33)12-17-14-29-21-10-6-4-8-19(17)21/h3-10,13-15,22-23,28-29H,11-12,27H2,1-2H3,(H,30,33)(H,31,35)(H,32,34)/t22-,23-/m1/s1

HIDE SMILES / InChI

Molecular Formula	C26H30N6O3
Molecular Weight	474.5558
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	2 / 2
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/205598s000lbl.pdf | https://www.drugbank.ca/drugs/DB13074

Macimorelin (AEZS 130) is an orally active, small-molecule, peptidomimetic growth hormone secretagogue receptor (GHSR1A) agonist (ghrelin analogue), being developed by AEterna Zentaris for the diagnosis of adult growth hormone deficiency (AGHD; somatotropin deficiency), and for the treatment of cachexia associated with chronic disease such as AIDS and cancer. Macimorelin was approved by the FDA in December 2017 under the market name Macrilen for oral solution. Macimorelin stimulates GH release by activating growth hormone secretagogue receptors present in the pituitary and hypothalamus. Macimorelin has been granted orphan drug designation by the FDA for diagnosis of AGHD.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Ghrelin receptor 15 Target ID: CHEMBL4616 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/205598s000lbl.pdf \| https://www.drugbank.ca/drugs/DB13074 \| https://www.ncbi.nlm.nih.gov/pubmed/23559086	Agonist 2470		123.0 nM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Growth hormone deficiency 5 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/205598s000lbl.pdf	Diagnostic		Approved 8043	MACRILEN Approved Use MACRILEN is a growth hormone (GH) secretagogue receptor agonist indicated for the diagnosis of adult growth hormone deficiency Launch Date 1.51364161E12

C_max

Value	Dose	Analyte	Population
9.24 ng/mL REVIEW https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/205598Orig1s000ClinPharmR.pdf	0.5 mg single, oral dose: 0.5 mg route of administration: Oral experiment type: SINGLE co-administered:	[NO STEREO] MACIMORELIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
10.6 μg/L REVIEW https://www.ema.europa.eu/en/documents/assessment-report/macimorelin-aeterna-zentaris-epar-public-assessment-report_en.pdf	0.5 mg/kg 1 times / day multiple, oral dose: 0.5 mg/kg route of administration: Oral experiment type: MULTIPLE co-administered:	[NO STEREO] MACIMORELIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
9.17 ng/mL REVIEW https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/205598Orig1s000ClinPharmR.pdf	0.5 mg/kg single, oral dose: 0.5 mg/kg route of administration: Oral experiment type: SINGLE co-administered:	MACIMORELIN plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
21.9 ng/mL REVIEW https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/205598Orig1s000ClinPharmR.pdf	2 mg/kg single, oral dose: 2 mg/kg route of administration: Oral experiment type: SINGLE co-administered:	MACIMORELIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

AUC

Value	Dose	Analyte	Population
38 ng × h/mL REVIEW https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/205598Orig1s000ClinPharmR.pdf	0.5 mg single, oral dose: 0.5 mg route of administration: Oral experiment type: SINGLE co-administered:	[NO STEREO] MACIMORELIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
32 μg × h/L REVIEW https://www.ema.europa.eu/en/documents/assessment-report/macimorelin-aeterna-zentaris-epar-public-assessment-report_en.pdf	0.5 mg/kg 1 times / day multiple, oral dose: 0.5 mg/kg route of administration: Oral experiment type: MULTIPLE co-administered:	[NO STEREO] MACIMORELIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
59.45 ng × h/mL REVIEW https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/205598Orig1s000ClinPharmR.pdf	0.5 mg/kg single, oral dose: 0.5 mg/kg route of administration: Oral experiment type: SINGLE co-administered:	MACIMORELIN plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
75.7 ng × h/mL REVIEW https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/205598Orig1s000ClinPharmR.pdf	2 mg/kg single, oral dose: 2 mg/kg route of administration: Oral experiment type: SINGLE co-administered:	MACIMORELIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

T_1/2

Value	Dose	Analyte	Population
3.51 h REVIEW https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/205598Orig1s000ClinPharmR.pdf	0.5 mg single, oral dose: 0.5 mg route of administration: Oral experiment type: SINGLE co-administered:	[NO STEREO] MACIMORELIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
3.9 h REVIEW https://www.ema.europa.eu/en/documents/assessment-report/macimorelin-aeterna-zentaris-epar-public-assessment-report_en.pdf	0.5 mg/kg 1 times / day multiple, oral dose: 0.5 mg/kg route of administration: Oral experiment type: MULTIPLE co-administered:	[NO STEREO] MACIMORELIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
3.76 h REVIEW https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/205598Orig1s000ClinPharmR.pdf	0.5 mg/kg single, oral dose: 0.5 mg/kg route of administration: Oral experiment type: SINGLE co-administered:	MACIMORELIN plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
7.23 h REVIEW https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/205598Orig1s000ClinPharmR.pdf	2 mg/kg single, oral dose: 2 mg/kg route of administration: Oral experiment type: SINGLE co-administered:	MACIMORELIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

F_unbound

Value	Dose	Co-administered	Analyte	Population
22% REVIEW https://www.ema.europa.eu/en/documents/assessment-report/macimorelin-aeterna-zentaris-epar-public-assessment-report_en.pdf	0.5 mg/kg 1 times / day multiple, oral dose: 0.5 mg/kg route of administration: Oral experiment type: MULTIPLE co-administered:		[NO STEREO] MACIMORELIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

Doses

Dose	Population	Adverse events
2 mg/kg 1 times / day single, oral Highest studied dose Dose: 2 mg/kg, 1 times / day Route: oral Route: single Dose: 2 mg/kg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/205598Orig1s000MedR.pdf Page: 205598Orig1s000MedR.pdf - p.124	healthy, adult n = 9 Health Status: healthy Age Group: adult Population Size: 9 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/205598Orig1s000MedR.pdf Page: 205598Orig1s000MedR.pdf - p.124	Other AEs: Diarrhoea, Pain... Other AEs: Diarrhoea (11.1%) Pain (11.1%) Headache (44.4%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/205598Orig1s000MedR.pdf Page: 205598Orig1s000MedR.pdf - p.124
0.5 mg/kg 1 times / day single, oral Recommended Dose: 0.5 mg/kg, 1 times / day Route: oral Route: single Dose: 0.5 mg/kg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/205598Orig1s000MedR.pdf Page: 205598Orig1s000MedR.pdf - p.124, p.52	unhealthy, adult n = 52 Health Status: unhealthy Condition: adult growth hormone deficiency Age Group: adult Population Size: 52 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/205598Orig1s000MedR.pdf Page: 205598Orig1s000MedR.pdf - p.124, p.52	Disc. AE: Vein collapse... AEs leading to discontinuation/dose reduction: Vein collapse (1.9%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/205598Orig1s000MedR.pdf Page: 205598Orig1s000MedR.pdf - p.124, p.52

AEs

AE	Significance	Dose	Population
Diarrhoea	11.1%	2 mg/kg 1 times / day single, oral Highest studied dose Dose: 2 mg/kg, 1 times / day Route: oral Route: single Dose: 2 mg/kg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/205598Orig1s000MedR.pdf Page: 205598Orig1s000MedR.pdf - p.124	healthy, adult n = 9 Health Status: healthy Age Group: adult Population Size: 9 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/205598Orig1s000MedR.pdf Page: 205598Orig1s000MedR.pdf - p.124
Pain	11.1%	2 mg/kg 1 times / day single, oral Highest studied dose Dose: 2 mg/kg, 1 times / day Route: oral Route: single Dose: 2 mg/kg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/205598Orig1s000MedR.pdf Page: 205598Orig1s000MedR.pdf - p.124	healthy, adult n = 9 Health Status: healthy Age Group: adult Population Size: 9 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/205598Orig1s000MedR.pdf Page: 205598Orig1s000MedR.pdf - p.124
Headache	44.4%	2 mg/kg 1 times / day single, oral Highest studied dose Dose: 2 mg/kg, 1 times / day Route: oral Route: single Dose: 2 mg/kg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/205598Orig1s000MedR.pdf Page: 205598Orig1s000MedR.pdf - p.124	healthy, adult n = 9 Health Status: healthy Age Group: adult Population Size: 9 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/205598Orig1s000MedR.pdf Page: 205598Orig1s000MedR.pdf - p.124
Vein collapse	1.9% Disc. AE	0.5 mg/kg 1 times / day single, oral Recommended Dose: 0.5 mg/kg, 1 times / day Route: oral Route: single Dose: 0.5 mg/kg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/205598Orig1s000MedR.pdf Page: 205598Orig1s000MedR.pdf - p.124, p.52	unhealthy, adult n = 52 Health Status: unhealthy Condition: adult growth hormone deficiency Age Group: adult Population Size: 52 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/205598Orig1s000MedR.pdf Page: 205598Orig1s000MedR.pdf - p.124, p.52

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1601 inhibitor 1467 inducer 707	inhibitor 1604 substrate 936	inhibitor 1702 substrate 1118	inhibitor 1475

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP1A2 1383 CYP2A6 627 CYP2C8 818 CYP2C19 1325 P-gp 1330	CYP1A1 325 CYP1A2 972 CYP2A6 485 CYP2B6 616 CYP2C8 634 CYP2C19 910 CYP2E1 606	CYP1A2 637 CYP2B6 501

Drug as perpetrator

Target	Modality	Activity
CYP2C19 1392	inhibitor 3045 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/205598Orig1s000ClinPharmR.pdf#page=35 Page: 35.0	no [IC50 25 uM]
CYP1A2 1532	inducer 1440 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/205598Orig1s000ClinPharmR.pdf#page=40 Page: 40.0	no
CYP1A2 1532	inhibitor 3045 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/205598Orig1s000ClinPharmR.pdf#page=35 Page: 35.0	no
CYP2A6 659	inhibitor 3045 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/205598Orig1s000ClinPharmR.pdf#page=35 Page: 35.0	no
CYP2C8 865	inhibitor 3045 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/205598Orig1s000ClinPharmR.pdf#page=35 Page: 35.0	no
CYP2C9 1648	inhibitor 3045 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/205598Orig1s000ClinPharmR.pdf#page=35 Page: 35.0	no
CYP2D6 1738	inhibitor 3045 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/205598Orig1s000ClinPharmR.pdf#page=35 Page: 35.0	no
P-gp 1514	inhibitor 3045 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/205598Orig1s000ClinPharmR.pdf#page=39 Page: 39.0	no
CYP2B6 884	inducer 1440 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/205598Orig1s000ClinPharmR.pdf#page=40 Page: 40.0	yes
CYP3A4 1772	inducer 1440 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/205598Orig1s000ClinPharmR.pdf#page=40 Page: 40.0	yes
CYP3A4 1772	inhibitor 3045 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/205598Orig1s000ClinPharmR.pdf#page=35 Page: 35.0	yes

Drug as victim

Target	Modality	Activity
CYP3A4 1601	substrate 3113 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/205598Orig1s000ClinPharmR.pdf#page=35 Page: 35.0	major
CYP1A1 325	substrate 3113 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/205598Orig1s000ClinPharmR.pdf#page=39 Page: 39.0	no
CYP1A2 972	substrate 3113 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/205598Orig1s000ClinPharmR.pdf#page=39 Page: 39.0	no
CYP2A6 485	substrate 3113 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/205598Orig1s000ClinPharmR.pdf#page=39 Page: 39.0	no
CYP2B6 616	substrate 3113 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/205598Orig1s000ClinPharmR.pdf#page=39 Page: 39.0	no
CYP2C19 910	substrate 3113 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/205598Orig1s000ClinPharmR.pdf#page=39 Page: 39.0	no
CYP2C8 634	substrate 3113 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/205598Orig1s000ClinPharmR.pdf#page=39 Page: 39.0	no
CYP2C9 936	substrate 3113 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/205598Orig1s000ClinPharmR.pdf#page=39 Page: 39.0	no
CYP2D6 1118	substrate 3113 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/205598Orig1s000ClinPharmR.pdf#page=39 Page: 39.0	no
CYP2E1 606	substrate 3113 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/205598Orig1s000ClinPharmR.pdf#page=39 Page: 39.0	no

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1507	inhibitor 1489 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/205598Orig1s000PharmR.pdf#page=28 Page: 28.0

Sourcing

Vendor/Aggregator	ID	URL
Chemieliva Pharmaceutical Co., Ltd	PBCM1293258
Compound Cloud	71526737
Compound Cloud	9804938
Hairui	HR139802	http://www.hairuichem.com/en/product/381231-18-1.html
Lan Pharmatech	LAN-B38700
Smolecule	S534360	http://www.smolecule.com/products/s534360
Stork BioChemicals	4LSC2025
Synblock Inc	SB16909	http://www.synblock.com/product/381231-18-1.html
THE BioTek	bt-274659	https://www.thebiotek.com/product/inhibitors/bt-274659
THE BioTek	bt-339764	https://www.thebiotek.com/product/others/bt-339764
ZINC	ZINC000001554197	http://zinc15.docking.org/substances/ZINC000001554197
iChemical	EBD3322128	http://www.ichemical.com/products/381231-18-1.html?utm_source=PubChem&utm_medium=website&utm_campaign=product%20catalogs

PubMed

Title	Date	PubMed
Effect of food on the pharmacokinetics and pharmacodynamics of an oral ghrelin agonist (ARD-07) in healthy subjects.	2009 May	19293342
Macimorelin (AEZS-130)-stimulated growth hormone (GH) test: validation of a novel oral stimulation test for the diagnosis of adult GH deficiency.	2013 Jun	23559086
The macimorelin-stimulated growth hormone test for adult growth hormone deficiency diagnosis.	2014 Jul	24834478

Patents

Sample Use Guides

In Vivo Use Guide

Recommended dose is 0.5 mg/kg as a single oral dose, after fasting for at least 8 hours

Route of Administration: Oral

In Vitro Use Guide

Macimorelin exhibited a high binding affinity to the cloned hGHS-R 1a receptor (IC50 value of 123 nM).

Substance Class	Chemical Created by `admin` on `Sat Jun 26 02:25:29 UTC 2021` Edited by `admin` on `Sat Jun 26 02:25:29 UTC 2021`
Record UNII	8680B21W73
Record Status	`Validated (UNII)`
Record Version

Download

Name

Type

Language

MACIMORELIN

Official Name

English

EP-1572

Code

English

MACIMORELIN [MI]

Common Name

English

D-87575

Code

English

JMV-1843

Code

English

ARD-07

Code

English

ARD 07

Code

English

N(SUP 2)-(2-AMINO-2-METHYLPROPANOYL-N1-((1R)-1-FORMAMIDO-2-(1H-INDOL-3-YL)ETHYL)-D-TRYPTOPHANAMIDE

Common Name

English

MACIMORELIN [USAN]

Common Name

English

AEZS-130

Code

English

MACIMORELIN [WHO-DD]

Common Name

English

EP-01572

Code

English

MACIMORELIN [INN]

Common Name

English

EP 1572

Code

English

Classification Tree Code System Code

WHO-ATC

V04CD06