MACIMORELIN ACETATE

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C26H30N6O3.C2H4O2
Molecular Weight	534.6068
Optical Activity	UNSPECIFIED
Defined Stereocenters	2 / 2
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CC(O)=O.CC(C)(N)C(=O)N[C@H](CC1=CNC2=C1C=CC=C2)C(=O)N[C@H](CC3=CNC4=C3C=CC=C4)NC=O

InChI

InChIKey=WVDSKQXKCDZXLH-OHIDFYLOSA-N

InChI=1S/C26H30N6O3.C2H4O2/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;1-2(3)4/h3-10,13-15,22-23,28-29H,11-12,27H2,1-2H3,(H,30,33)(H,31,35)(H,32,34);1H3,(H,3,4)/t22-,23-;/m1./s1

HIDE SMILES / InChI

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 2678		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 8429	MACRILEN Approved Use MACRILEN is a growth hormone (GH) secretagogue receptor agonist indicated for the diagnosis of adult growth hormone deficiency Launch Date 2017

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 1737 inhibitor 1587 inducer 781	inhibitor 1767 substrate 1037	inhibitor 1852 substrate 1217	inhibitor 1612

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP1A2 1524 CYP2A6 707 CYP2C8 911 CYP2C19 1478 P-gp 1461	CYP1A1 349 CYP1A2 1054 CYP2A6 543 CYP2B6 664 CYP2C8 693 CYP2C19 991 CYP2E1 667	CYP1A2 701 CYP2B6 547

Drug as perpetrator

Target	Modality	Activity
CYP2C19 1553	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/205598Orig1s000ClinPharmR.pdf#page=35 Page: 35.0	no [IC50 25 uM]
CYP1A2 1692	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/205598Orig1s000ClinPharmR.pdf#page=40 Page: 40.0	no
CYP1A2 1692	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/205598Orig1s000ClinPharmR.pdf#page=35 Page: 35.0	no
CYP2A6 739	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/205598Orig1s000ClinPharmR.pdf#page=35 Page: 35.0	no
CYP2C8 965	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/205598Orig1s000ClinPharmR.pdf#page=35 Page: 35.0	no
CYP2C9 1819	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/205598Orig1s000ClinPharmR.pdf#page=35 Page: 35.0	no
CYP2D6 1891	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/205598Orig1s000ClinPharmR.pdf#page=35 Page: 35.0	no
P-gp 1650	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/205598Orig1s000ClinPharmR.pdf#page=39 Page: 39.0	no
CYP2B6 1001	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/205598Orig1s000ClinPharmR.pdf#page=40 Page: 40.0	yes
CYP3A4 1925	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/205598Orig1s000ClinPharmR.pdf#page=40 Page: 40.0	yes
CYP3A4 1925	inhibitor 3277 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 1737	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/205598Orig1s000ClinPharmR.pdf#page=35 Page: 35.0	major
CYP1A1 349	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/205598Orig1s000ClinPharmR.pdf#page=39 Page: 39.0	no
CYP1A2 1054	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/205598Orig1s000ClinPharmR.pdf#page=39 Page: 39.0	no
CYP2A6 543	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/205598Orig1s000ClinPharmR.pdf#page=39 Page: 39.0	no
CYP2B6 664	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/205598Orig1s000ClinPharmR.pdf#page=39 Page: 39.0	no
CYP2C19 991	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/205598Orig1s000ClinPharmR.pdf#page=39 Page: 39.0	no
CYP2C8 693	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/205598Orig1s000ClinPharmR.pdf#page=39 Page: 39.0	no
CYP2C9 1037	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/205598Orig1s000ClinPharmR.pdf#page=39 Page: 39.0	no
CYP2D6 1217	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/205598Orig1s000ClinPharmR.pdf#page=39 Page: 39.0	no
CYP2E1 667	substrate 3367 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 1647	inhibitor 1626 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).

Name

Type

Language

MACIMORELIN ACETATE

Official Name

English

EP-1572 ACETATE

Code

English

MACIMORELIN ACETATE [ORANGE BOOK]

Common Name

English

MACIMORELIN ACETATE [USAN]

Common Name

English

MACIMORELIN ACETATE [MI]

Common Name

English

Macimorelin acetate [WHO-DD]

Common Name

English

ARD-07 ACETATE

Code

English

MACRILEN

Brand Name

English

N2-(2-AMINO-2-METHYLPROPANOYL-N1-((1R)-1-FORMAMIDO-2-(1H-INDOL-3-YL)ETHYL)- D-TRYPTOPHANAMIDE ACETATE

Common Name

English

D-TRYPTOPHANAMIDE, 2-METHYLALANYL-N-((1R)-1-(FORMYLAMINO)-2-(1H-INDOL-3-YL)ETHYL)-, ACETATE (1:1)

Systematic Name

English

D-87575 ACETATE

Code

English

Classification Tree Code System Code

FDA ORPHAN DRUG

225506