tabimorelin

{{Short description|Chemical compound}}

{{Drugbox

| verifiedrevid = 450106371

| IUPAC_name = N-[(2E)-5-amino-5-methylhex-enoyl]-N-methyl-3-(2-naphthyl)alanyl-N,Nα-dimethyl-D-phenylalaninamide

| image = Tabimorelin skeletal.svg

| tradename =

| pregnancy_AU =

| pregnancy_US =

| legal_AU =

| legal_UK =

| legal_US =

| routes_of_administration =

| bioavailability =

| protein_bound =

| metabolism =

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| CAS_number_Ref = {{cascite|correct|CAS}}

| CAS_number = 193079-69-5

| ATC_prefix = none

| ATC_suffix =

| ATC_supplemental =

| PubChem = 9810101

| DrugBank_Ref = {{drugbankcite|correct|drugbank}}

| DrugBank =

| ChemSpiderID = 7985857

| UNII_Ref = {{fdacite|correct|FDA}}

| UNII = L51CBE03KF

| C=32 | H=40 | N=4 | O=3

| smiles = CC(C)(C/C=C/C(=O)N(C)[C@H](CC1=CC2=CC=CC=C2C=C1)C(=O)N(C)[C@H](CC3=CC=CC=C3)C(=O)NC)N

| StdInChI = 1S/C32H40N4O3/c1-32(2,33)19-11-16-29(37)35(4)28(22-24-17-18-25-14-9-10-15-26(25)20-24)31(39)36(5)27(30(38)34-3)21-23-12-7-6-8-13-23/h6-18,20,27-28H,19,21-22,33H2,1-5H3,(H,34,38)/b16-11+/t27-,28-/m1/s1

| StdInChIKey = WURGZWOTGMLDJP-ZCYANPAGSA-N

| synonyms = ((2E)-5-amino-5-methylhex-2-enoic acid N-methyl-N-((1R)-1-(N-methyl-N-((1R)-1-(methylcarbamoyl)-2-phenylethyl)carbamoyl)-2-(2-naphthyl)ethyl)amide)

}}

Tabimorelin (INN) (developmental code name NN-703) is a drug which acts as a potent, orally-active agonist of the ghrelin/growth hormone secretagogue receptor (GHSR) and growth hormone secretagogue, mimicking the effects of the endogenous peptide agonist ghrelin as a stimulator of growth hormone (GH) release. It was one of the first GH secretagogues developed and is largely a modified polypeptide, but it is nevertheless orally-active in vivo.{{cite journal | vauthors = Hansen BS, Raun K, Nielsen KK, Johansen PB, Hansen TK, Peschke B, Lau J, Andersen PH, Ankersen M | display-authors = 6 | title = Pharmacological characterisation of a new oral GH secretagogue, NN703 | journal = European Journal of Endocrinology | volume = 141 | issue = 2 | pages = 180–9 | date = August 1999 | pmid = 10427162 | doi = 10.1530/eje.0.1410180 | doi-access = free }} Tabimorelin produced sustained increases in levels of GH and insulin-like growth factor 1 (IGF-1), along with smaller transient increases in levels of other hormones such as adrenocorticotropic hormone (ACTH), cortisol, and prolactin.{{cite journal | vauthors = Zdravkovic M, Søgaard B, Ynddal L, Christiansen T, Agersø H, Thomsen MS, Falch JE, Ilondo MM | display-authors = 6 | title = The pharmacokinetics, pharmacodynamics, safety and tolerability of a single dose of NN703, a novel orally active growth hormone secretagogue in healthy male volunteers | journal = Growth Hormone & IGF Research | volume = 10 | issue = 4 | pages = 193–8 | date = August 2000 | pmid = 11032702 | doi = 10.1054/ghir.2000.0152 }}{{cite journal | vauthors = Zdravkovic M, Christiansen T, Eliot L, Agersoe H, Thomsen MS, Falch JF, Søgaard B, Ynddal L, Ilondo MM | display-authors = 6 | title = The pharmacokinetics, pharmacodynamics, safety and tolerability following 7 days daily oral treatment with NN703 in healthy male subjects | journal = Growth Hormone & IGF Research | volume = 11 | issue = 1 | pages = 41–8 | date = February 2001 | pmid = 11437473 | doi = 10.1054/ghir.2000.0188 }} However actual clinical effects in adults with growth hormone deficiency were limited, with only the most severely GH-deficient patients showing significant benefit,{{cite journal | vauthors = Svensson J, Monson JP, Vetter T, Hansen TK, Savine R, Kann P, Bex M, Reincke M, Hagen C, Beckers A, Ilondo MM, Zdravkovic M, Bengtsson BA, Korbonits M | display-authors = 6 | title = Oral administration of the growth hormone secretagogue NN703 in adult patients with growth hormone deficiency | journal = Clinical Endocrinology | volume = 58 | issue = 5 | pages = 572–80 | date = May 2003 | pmid = 12699438 | doi = 10.1046/j.1365-2265.2003.01754.x | s2cid = 33510538 }} and tabimorelin was also found to act as a CYP3A4 inhibitor which could cause it to have undesirable interactions with other drugs.{{cite journal | vauthors = Zdravkovic M, Olsen AK, Christiansen T, Schulz R, Taub ME, Thomsen MS, Rasmussen MH, Ilondo MM | display-authors = 6 | title = A clinical study investigating the pharmacokinetic interaction between NN703 (tabimorelin), a potential inhibitor of CYP3A4 activity, and midazolam, a CYP3A4 substrate | journal = European Journal of Clinical Pharmacology | volume = 58 | issue = 10 | pages = 683–8 | date = February 2003 | pmid = 12610745 | doi = 10.1007/s00228-002-0539-1 | s2cid = 22546247 }}