Acyline

Chemical compound

Acyline
Clinical data

Other names	MER-104
Routes of administration	Subcutaneous injection^[1]^[2]
Drug class	GnRH antagonist
Identifiers
IUPAC name (2S)-1-[(2S)-2-[[(2S)-2-[[(2R)-2-[[(2S)-2-[[(2S)-2-[[(2R)-2-[[(2R)-2-[[(2R)-2-acetamido-3-naphthalen-2-ylpropanoyl]amino]-3-(4-chlorophenyl)propanoyl]amino]-3-pyridin-3-ylpropanoyl]amino]-3-hydroxypropanoyl]amino]-3-(4-acetamidophenyl)propanoyl]amino]-3-(4-acetamidophenyl)propanoyl]amino]-4-methylpentanoyl]amino]-6-(propan-2-ylamino)hexanoyl]-N-[(2R)-1-amino-1-oxopropan-2-yl]pyrrolidine-2-carboxamide
CAS Number	170157-13-8
PubChem CID	16137348
DrugBank	DB11906
ChemSpider	17293858
UNII	S3439D3B35
ChEMBL	ChEMBL262747
CompTox Dashboard (EPA)	DTXSID60168812
Chemical and physical data
Formula	C₈₀H₁₀₂ClN₁₅O₁₄
Molar mass	1533.24 g·mol⁻¹
3D model (JSmol)	Interactive image
SMILES C[C@H](C(=O)N)NC(=O)[C@@H]1CCCN1C(=O)[C@H](CCCCNC(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](CC2=CC=C(C=C2)NC(=O)C)NC(=O)[C@H](CC3=CC=C(C=C3)NC(=O)C)NC(=O)[C@H](CO)NC(=O)[C@@H](CC4=CN=CC=C4)NC(=O)[C@@H](CC5=CC=C(C=C5)Cl)NC(=O)[C@@H](CC6=CC7=CC=CC=C7C=C6)NC(=O)C
InChI InChI=1S/C80H102ClN15O14/c1-46(2)37-63(72(102)89-62(18-11-12-35-84-47(3)4)80(110)96-36-14-19-70(96)79(109)85-48(5)71(82)101)90-74(104)66(40-53-23-30-60(31-24-53)86-49(6)98)92-76(106)67(41-54-25-32-61(33-26-54)87-50(7)99)94-78(108)69(45-97)95-77(107)68(43-56-15-13-34-83-44-56)93-75(105)65(39-52-21-28-59(81)29-22-52)91-73(103)64(88-51(8)100)42-55-20-27-57-16-9-10-17-58(57)38-55/h9-10,13,15-17,20-34,38,44,46-48,62-70,84,97H,11-12,14,18-19,35-37,39-43,45H2,1-8H3,(H2,82,101)(H,85,109)(H,86,98)(H,87,99)(H,88,100)(H,89,102)(H,90,104)(H,91,103)(H,92,106)(H,93,105)(H,94,108)(H,95,107)/t48-,62+,63+,64-,65-,66-,67+,68-,69+,70+/m1/s1 Key:ZWNUQDJANZGVFO-YHSALVGYSA-N

Acyline (developmental code name MER-104) is a gonadotropin-releasing hormone analogue (GnRH analogue) and gonadotropin-releasing hormone antagonist (GnRH antagonist) which was never marketed.^[1]^[2]^[3] It has been shown to suppress gonadotropin and testosterone levels in men.^[1]^[2]^[3] Acyline is a peptide and under normal circumstances is not orally active.^[3] For this reason, it has instead been administered by subcutaneous injection.^[1]^[2]

References

^ ^a ^b ^c ^d Herbst KL, Anawalt BD, Amory JK, Bremner WJ (July 2002). "Acyline: the first study in humans of a potent, new gonadotropin-releasing hormone antagonist". J. Clin. Endocrinol. Metab. 87 (7): 3215–20. doi:10.1210/jcem.87.7.8675. hdl:1773/4394. PMID 12107227.
^ ^a ^b ^c ^d Herbst KL, Coviello AD, Page S, Amory JK, Anawalt BD, Bremner WJ (December 2004). "A single dose of the potent gonadotropin-releasing hormone antagonist acyline suppresses gonadotropins and testosterone for 2 weeks in healthy young men". J. Clin. Endocrinol. Metab. 89 (12): 5959–65. doi:10.1210/jc.2003-032123. hdl:1773/4325. PMID 15579744.
^ ^a ^b ^c Amory JK, Leonard TW, Page ST, O'Toole E, McKenna MJ, Bremner WJ (August 2009). "Oral administration of the GnRH antagonist acyline, in a GIPET-enhanced tablet form, acutely suppresses serum testosterone in normal men: single-dose pharmacokinetics and pharmacodynamics". Cancer Chemother. Pharmacol. 64 (3): 641–5. doi:10.1007/s00280-009-1038-1. PMC 2721900. PMID 19479252.

GnRHTooltip Gonadotropin-releasing hormone and gonadotropins

GnRH modulators
(incl. analogues)

Agonists	Peptide: Azagly-nafarelin Buserelin Deslorelin Fertirelin Gonadorelin Goserelin Histrelin Lecirelin Leuprorelin (leuprolide) Nafarelin Peforelin Triptorelin
Antagonists	Peptide: Abarelix Cetrorelix Degarelix Ganirelix Non-peptide: Elagolix Linzagolix^† Relugolix (+estradiol/norethisterone acetate)

Gonadotropins

Preparations	Follicle-stimulating hormone Human chorionic gonadotropin Luteinizing hormone Menotropin Urofollitropin

Others
(indirect)

Progonadotropins	Sex steroid antagonists (via disinhibition of the HPG axis): Antiandrogens (e.g., flutamide, bicalutamide, enzalutamide) Antiestrogens/SERMsTooltip Selective estrogen receptor modulators (e.g., tamoxifen, clomifene, enclomifene) Aromatase inhibitors (e.g., anastrozole) GnRH agonists (e.g., GnRHTooltip gonadotropin-releasing hormone)
Antigonadotropins	Sex steroid agonists (via negative feedback on the HPG axis): Androgens/anabolic steroids (e.g., testosterone, nandrolone esters, oxandrolone) D₂ receptor antagonists (prolactin releasers) (incl., domperidone, metoclopramide, risperidone, haloperidol, chlorpromazine, sulpiride) Estrogens (incl., bifluranol, estradiol, estradiol esters, ethinylestradiol, diethylstilbestrol, paroxypropione) Progestogens (incl. progestins, e.g., chlormadinone acetate, cyproterone acetate, hydroxyprogesterone caproate, gestonorone caproate, medroxyprogesterone acetate, megestrol acetate) Others (mixed or unknown mechanism of action): Danazol Gestrinone Metallibure

Progonadotropins

Sex steroid antagonists (via disinhibition of the HPG axis): Antiandrogens (e.g., flutamide, bicalutamide, enzalutamide)
Antiestrogens/SERMsTooltip Selective estrogen receptor modulators (e.g., tamoxifen, clomifene, enclomifene)
Aromatase inhibitors (e.g., anastrozole)
GnRH agonists (e.g., GnRHTooltip gonadotropin-releasing hormone)

Antigonadotropins

Sex steroid agonists (via negative feedback on the HPG axis): Androgens/anabolic steroids (e.g., testosterone, nandrolone esters, oxandrolone)
D₂ receptor antagonists (prolactin releasers) (incl., domperidone, metoclopramide, risperidone, haloperidol, chlorpromazine, sulpiride)
Estrogens (incl., bifluranol, estradiol, estradiol esters, ethinylestradiol, diethylstilbestrol, paroxypropione)
Progestogens (incl. progestins, e.g., chlormadinone acetate, cyproterone acetate, hydroxyprogesterone caproate, gestonorone caproate, medroxyprogesterone acetate, megestrol acetate)

Others (mixed or unknown mechanism of action): Danazol
Gestrinone
Metallibure

^#WHO-EM
^‡Withdrawn from market
Clinical trials:
- ^†Phase III
- ^§Never to phase III

See also: GnRH and gonadotropin receptor modulators; Androgens and antiandrogens; Estrogens and antiestrogens; Progestogens and antiprogestogens

GnRHTooltip Gonadotropin-releasing hormone receptor and gonadotropin receptor modulators

GnRHTooltip Gonadotropin-releasing hormone receptor

Agonists: Peptides: Alarelin
Avorelin
Azagly-nafarelin
Buserelin
Deslorelin
Fertirelin
GnRH
Gonadorelin
Goserelin
Histrelin
Leuprorelin (leuprolide)
Lutrelin
Nafarelin
Peforelin
Salmon GnRH
Triptorelin
Zoptarelin
Zoptarelin doxorubicin

Antagonists: Peptides: Abarelix
Acyline
Azaline B
Cetrorelix
Degarelix
Detirelix
Ganirelix
Iturelix (antide)
LXT-101
Ornirelix (ornitide)
Ozarelix
Prazarelix
Ramorelix
Teverelix (antarelix); Non-peptides: Elagolix
Linzagolix
Opigolix
Relugolix
Sufugolix

Gonadotropin

LH/hCGTooltip Luteinizing hormone/choriogonadotropin receptor	Agonists: Peptides: Choriogonadotropin alfa Human chorionic gonadotropin Luteinizing hormone Lutropin alfa Menotropin (human menopausal gonadotropin)
FSHTooltip Follicle-stimulating hormone receptor	Agonists: Peptides: Corifollitropin alfa Follicle-stimulating hormone Follitropin alfa Follitropin beta Follitropin epsilon Menotropin (human menopausal gonadotropin) Urofollitropin Varfollitropin alfa NAMs: Non-peptides: ADX-61623