Absorption, Distribution and Excretion
Rapid absorption after intramuscular injection. Cosyntropin is rapidly absorbed after intramuscular injection. Tetracosactrin adsorbs onto zinc phosphate, allowing for sustained release of the active substance from the injection site. Following intramuscular injection of 1 mg of the extended-release tetracosactin (Synacthen Depot), plasma tetracosactin concentrations, as measured by radioimmunoassay, remained between 200 and 300 pg/mL over 12 hours. The apparent volume of distribution of tetracosactin is approximately 0.4 L/kg. /Tetracosactin-Zinc Phosphate Complex Extended-Release (Not Marketed in the US)/ The exact distribution and metabolic pathways of corticotropin are unclear, but the drug is rapidly cleared from plasma by various tissues. Corticotropin apparently does not cross the placenta. Biological Half-Life Approximately 15 minutes after intravenous injection.

[1]. Adding Slow Release Tetracosactide Acetate to Eltrombopag Improves Haematological Response in ITP Patients with Platelet-Count Fluctuation. 2018 Nov 29;132(1).

Tetracosactide (also known as Cosyntropin) is a synthetic peptide identical to the N-terminal 24 amino acid fragment of adrenocorticotropic hormone (ACTH) (sequence: SYSMEHFRWGKPVGKKRRPVKVYP). ACTH(1-24) is a similar fragment across all species and possesses the biological activity of stimulating the adrenal cortex to produce corticosteroids. Tetracosactide is identical to natural ACTH in all its biological activities. Compared to ACTH, this complex has a longer duration of absorption in the body. Therefore, the frequency of administration can be reduced to maintain treatment. Cosyntropin is a synthetically derived subunit of the endogenous pituitary hormone adrenocorticotropic hormone (ACTH). Composed of the first 24 amino acids from the N-terminus of ACTH, Cosyntropin is typically formulated as an injectable drug for diagnostic rather than therapeutic purposes. Similar to endogenous ACTH, this drug stimulates the adrenal glands to secrete specific adrenocortical hormones, which can be detected in plasma. (NCI04)
A synthetic peptide identical to the N-terminal 24-amino acid fragment of adrenocorticotropic hormone (ACTH). ACTH (1-24) is a similar peptide in all species, possessing the biological activity of stimulating the adrenal cortex to produce corticosteroids.

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Pharmacological Indications
For screening and diagnosis of suspected adrenocortical insufficiency.

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Mechanism of Action
ACTH binds to specific receptors on the adrenal cell membrane. In patients with normal adrenal cortical function, it stimulates an initial response to cholesterol-derived adrenal steroids (including cortisol, cortisone, weak androgens, and small amounts of aldosterone) by increasing the amount of substrates within the mitochondria. In patients with primary or secondary adrenocortical insufficiency, ACTH does not significantly increase plasma cortisol concentrations. Corticotropin (ACT) elicits all the pharmacological responses typically produced by endogenous ACTP; however, ACTP's immunomodulatory activity is far lower than that of adrenocorticotropic hormone (ACTH) because most of ACTP's antigenic activity is attributed to the C-terminal portion of its molecule (amino acid residues 22-39). In patients with normal adrenal cortex function, ACTP stimulates the adrenal cortex to secrete cortisol (hydrocortisone), corticosterone, several weak androgens, and small amounts of aldosterone. When ACTP is used for diagnosis, its effect is usually assessed by measuring plasma cortisol concentrations before and after administration. In patients with primary adrenal insufficiency (Addie's disease), ACTP does not significantly increase plasma cortisol concentrations.

C136H210N40O31S

2933.4370

2931.58

16960-16-0

Tetracosactide acetate;60189-34-6

16133802

White to off-white solid powder

1.5±0.1 g/cm3

1.681

-3.27

42

41

96

208

6500

22

S(C([H])([H])[H])C([H])([H])C([H])([H])[C@@]([H])(C(N([H])[C@@]([H])(C([H])([H])C([H])([H])C(=O)O[H])C(N([H])[C@@]([H])(C([H])([H])C1=C([H])N([H])C([H])=N1)C(N([H])[C@@]([H])(C([H])([H])C1C([H])=C([H])C([H])=C([H])C=1[H])C(N([H])[C@@]([H])(C([H])([H])C([H])([H])C([H])([H])N([H])/C(=N/[H])/N([H])[H])C(N([H])[C@@]([H])(C([H])([H])C1=C([H])N([H])C2=C([H])C([H])=C([H])C([H])=C12)C(N([H])C([H])([H])C(N([H])[C@@]([H])(C([H])([H])C([H])([H])C([H])([H])C([H])([H])N([H])[H])C(N1C([H])([H])C([H])([H])C([H])([H])[C@@]1([H])C(N([H])[C@]([H])(C(N([H])C([H])([H])C(N([H])[C@@]([H])(C([H])([H])C([H])([H])C([H])([H])C([H])([H])N([H])[H])C(N([H])[C@@]([H])(C([H])([H])C([H])([H])C([H])([H])C([H])([H])N([H])[H])C(N([H])[C@@]([H])(C([H])([H])C([H])([H])C([H])([H])N([H])/C(=N/[H])/N([H])[H])C(N([H])[C@@]([H])(C([H])([H])C([H])([H])C([H])([H])N([H])/C(=N/[H])/N([H])[H])C(N1C([H])([H])C([H])([H])C([H])([H])[C@@]1([H])C(N([H])[C@]([H])(C(N([H])[C@]([H])(C(N([H])[C@]([H])(C(N([H])[C@@]([H])(C([H])([H])C1C([H])=C([H])C(=C([H])C=1[H])O[H])C(N1C([H])([H])C([H])([H])C([H])([H])[C@@]1([H])C(=O)O[H])=O)=O)C([H])(C([H])([H])[H])C([H])([H])[H])=O)C([H])([H])C([H])([H])C([H])([H])C([H])([H])N([H])[H])=O)C([H])(C([H])([H])[H])C([H])([H])[H])=O)=O)=O)=O)=O)=O)=O)C([H])(C([H])([H])[H])C([H])([H])[H])=O)=O)=O)=O)=O)=O)=O)=O)=O)N([H])C([C@]([H])(C([H])([H])O[H])N([H])C([C@]([H])(C([H])([H])C1C([H])=C([H])C(=C([H])C=1[H])O[H])N([H])C([C@]([H])(C([H])([H])O[H])N([H])[H])=O)=O)=O

ZOEFCCMDUURGSE-SQKVDDBVSA-N

InChI=1S/C136H210N40O31S/c1-75(2)109(127(200)154-71-106(181)156-88(31-13-17-52-137)114(187)158-89(32-14-18-53-138)115(188)159-91(35-21-56-149-134(142)143)116(189)164-96(37-23-58-151-136(146)147)131(204)175-60-25-39-104(175)126(199)173-111(77(5)6)128(201)163-90(33-15-19-54-139)120(193)171-110(76(3)4)129(202)169-101(65-80-43-47-84(180)48-44-80)132(205)176-61-26-40-105(176)133(206)207)172-125(198)103-38-24-59-174(103)130(203)95(34-16-20-55-140)157-107(182)70-153-113(186)99(66-81-68-152-87-30-12-11-29-85(81)87)167-117(190)92(36-22-57-150-135(144)145)160-121(194)98(63-78-27-9-8-10-28-78)166-123(196)100(67-82-69-148-74-155-82)168-118(191)93(49-50-108(183)184)161-119(192)94(51-62-208-7)162-124(197)102(73-178)170-122(195)97(165-112(185)86(141)72-177)64-79-41-45-83(179)46-42-79/h8-12,27-30,41-48,68-69,74-77,86,88-105,109-111,152,177-180H,13-26,31-40,49-67,70-73,137-141H2,1-7H3,(H,148,155)(H,153,186)(H,154,200)(H,156,181)(H,157,182)(H,158,187)(H,159,188)(H,160,194)(H,161,192)(H,162,197)(H,163,201)(H,164,189)(H,165,185)(H,166,196)(H,167,190)(H,168,191)(H,169,202)(H,170,195)(H,171,193)(H,172,198)(H,173,199)(H,183,184)(H,206,207)(H4,142,143,149)(H4,144,145,150)(H4,146,147,151)/t86-,88-,89-,90-,91-,92-,93-,94-,95-,96-,97-,98-,99-,100-,101-,102-,103-,104-,105-,109-,110-,111-/m0/s1

(2S)-1-[(2S)-2-[[(2S)-2-[[(2S)-6-amino-2-[[(2S)-2-[[(2S)-1-[(2S)-2-[[(2S)-2-[[(2S)-6-amino-2-[[(2S)-6-amino-2-[[2-[[(2S)-2-[[(2S)-1-[(2S)-6-amino-2-[[2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-amino-3-hydroxypropanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-3-hydroxypropanoyl]amino]-4-methylsulfanylbutanoyl]amino]-4-carboxybutanoyl]amino]-3-(1H-imidazol-4-yl)propanoyl]amino]-3-phenylpropanoyl]amino]-5-carbamimidamidopentanoyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]acetyl]amino]hexanoyl]pyrrolidine-2-carbonyl]amino]-3-methylbutanoyl]amino]acetyl]amino]hexanoyl]amino]hexanoyl]amino]-5-carbamimidamidopentanoyl]amino]-5-carbamimidamidopentanoyl]pyrrolidine-2-carbonyl]amino]-3-methylbutanoyl]amino]hexanoyl]amino]-3-methylbutanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]pyrrolidine-2-carboxylic acid

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture and light.

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

H2O : ~100 mg/mL (~34.09 mM)

Solubility in Formulation 1: 100 mg/mL (34.09 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with sonication.

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 (Please use freshly prepared in vivo formulations for optimal results.)