Details of the Drug

General Information of Drug (ID: DMP9TWZ)

• Drug Name: Corticotropin
• Synonyms: corticotropin; ACTH; Cortrophin; Corticotrophin; Adrenocorticotropic hormone; Corticotrophine; Corticotrofina; Acthargel; Corticotrophinum; beta-Corticotropin; Adrenocorticotrophin; Purified Cortrophin gel; Corticotropin [USP:INN]; 9002-60-2; CHEBI:3892; BDBM82408; ACTH-(1-39); 25-Asp-30-Gln-corticotropin porcine; NCGC00167127-01; CAS_12279-41-3; Adrenocorticotropic Hormone (1-39), human; LS-187380; SYSMEHFRWGKPVGKKRRPVKVYPDGAEDQLAEAFPLEF; J-004856; alpha1-39-Corticotropin (swine), 25-L-aspartic acid-30-L-glutamine

Indication

Disease Entry	ICD 11	Status	REF
Cushing disease	5A70	Approved	[1], [2]
Diabetic nephropathy	GB61.Z	Approved	[3], [4]

• Sequence: SYSMEHFRWGKPVGKKRRPVKVYPDGAEDQLAEAFPLEF
• #Ro5 Violations (Lipinski): 5:
  Molecular Weight (mw); 4541
  Topological Polar Surface Area (xlogp); -19.7
  Rotatable Bond Count (rotbonds); 148
  Hydrogen Bond Donor Count (hbonddonor); 63
  Hydrogen Bond Acceptor Count (hbondacc); 68
• ADMET Property: Half-life: The concentration or amount of drug in body reduced by one-half in 15 minutes [5]
• Chemical Identifiers:
  Formula: C207H308N56O58S
  IUPAC Name: (4S)-4-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[2-[[(2S)-4-amino-2-[[(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-5-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-carbonyl]amino]-4-oxobutanoyl]amino]acetyl]amino]propanoyl]amino]-4-carboxybutanoyl]amino]-3-carboxypropanoyl]amino]-4-carboxybutanoyl]amino]-3-hydroxypropanoyl]amino]propanoyl]amino]-5-[[(2S)-1-[[(2S)-1-[(2S)-2-[[(2S)-1-[[(2S)-4-carboxy-1-[[(1S)-1-carboxy-2-phenylethyl]amino]-1-oxobutan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]carbamoyl]pyrrolidin-1-yl]-1-oxo-3-phenylpropan-2-yl]amino]-1-oxopropan-2-yl]amino]-5-oxopentanoic acid
  Canonical SMILES: C[C@@H](C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CO)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N2CCC[C@H]2C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC3=CC=CC=C3)C(=O)O)NC(=O)CNC(=O)[C@H](CC(=O)N)NC(=O)[C@@H]4CCCN4C(=O)[C@H](CC5=CC=C(C=C5)O)NC(=O)[C@H](C(C)C)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C(C)C)NC(=O)[C@@H]6CCCN6C(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCCCN)NC(=O)CNC(=O)[C@H](C(C)C)NC(=O)[C@@H]7CCCN7C(=O)[C@H](CCCCN)NC(=O)CNC(=O)[C@H](CC8=CNC9=CC=CC=C98)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CC1=CC=CC=C1)NC(=O)[C@H](CC1=CN=CN1)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCSC)NC(=O)[C@H](CO)NC(=O)[C@H](CC1=CC=C(C=C1)O)NC(=O)[C@H](CO)N
  InChI: InChI=1S/C207H308N56O58S/c1-108(2)89-140(186(302)240-135(69-74-163(279)280)182(298)254-149(204(320)321)94-117-43-20-15-21-44-117)250-193(309)152-54-35-86-262(152)202(318)147(92-116-41-18-14-19-42-116)252-171(287)114(11)230-175(291)132(66-71-160(273)274)234-170(286)113(10)231-191(307)150(105-265)255-183(299)136(70-75-164(281)282)241-190(306)146(98-165(283)284)249-180(296)133(67-72-161(275)276)235-169(285)112(9)229-157(270)101-225-174(290)145(97-156(213)269)251-194(310)153-55-36-87-263(153)203(319)148(93-119-60-64-123(268)65-61-119)253-199(315)167(110(5)6)257-185(301)129(49-26-30-79-210)243-198(314)168(111(7)8)259-196(312)155-57-38-85-261(155)201(317)139(53-34-83-223-207(218)219)244-178(294)130(51-32-81-221-205(214)215)237-177(293)128(48-25-29-78-209)236-176(292)127(47-24-28-77-208)232-158(271)103-227-197(313)166(109(3)4)258-195(311)154-56-37-84-260(154)200(316)138(50-27-31-80-211)233-159(272)102-226-173(289)143(95-120-99-224-126-46-23-22-45-124(120)126)247-179(295)131(52-33-82-222-206(216)217)238-187(303)142(90-115-39-16-13-17-40-115)246-189(305)144(96-121-100-220-107-228-121)248-181(297)134(68-73-162(277)278)239-184(300)137(76-88-322-12)242-192(308)151(106-266)256-188(304)141(245-172(288)125(212)104-264)91-118-58-62-122(267)63-59-118/h13-23,39-46,58-65,99-100,107-114,125,127-155,166-168,224,264-268H,24-38,47-57,66-98,101-106,208-212H2,1-12H3,(H2,213,269)(H,220,228)(H,225,290)(H,226,289)(H,227,313)(H,229,270)(H,230,291)(H,231,307)(H,232,271)(H,233,272)(H,234,286)(H,235,285)(H,236,292)(H,237,293)(H,238,303)(H,239,300)(H,240,302)(H,241,306)(H,242,308)(H,243,314)(H,244,294)(H,245,288)(H,246,305)(H,247,295)(H,248,297)(H,249,296)(H,250,309)(H,251,310)(H,252,287)(H,253,315)(H,254,298)(H,255,299)(H,256,304)(H,257,301)(H,258,311)(H,259,312)(H,273,274)(H,275,276)(H,277,278)(H,279,280)(H,281,282)(H,283,284)(H,320,321)(H4,214,215,221)(H4,216,217,222)(H4,218,219,223)/t112-,113-,114-,125-,127-,128-,129-,130-,131-,132-,133-,134-,135-,136-,137-,138-,139-,140-,141-,142-,143-,144-,145-,146-,147-,148-,149-,150-,151-,152-,153-,154-,155-,166-,167-,168-/m0/s1
  InChIKey: IDLFZVILOHSSID-OVLDLUHVSA-N
• Cross-matching ID:
  PubChem CID: 16132265
  ChEBI ID: CHEBI:3892
  CAS Number: 12427-33-7
  DrugBank ID: DB01285
  TTD ID: D0R4HQ
  INTEDE ID: DR0383

Molecular Interaction Atlas of This Drug

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 3A4 (CYP3A4) Main DME	DE4LYSA	CP3A4_HUMAN	Substrate	[6]

Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Disease Different from Corticotropin (Comorbidity)

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Comorbidity	REF
Levalbuterol	DM5YBO1	Minor	Increased risk of hypokalemia by the combination of Corticotropin and Levalbuterol.	Asthma [CA23]	[16]
Pirbuterol	DMI5678	Minor	Increased risk of hypokalemia by the combination of Corticotropin and Pirbuterol.	Asthma [CA23]	[17]
Roflumilast	DMPGHY8	Moderate	Additive immunosuppressive effects by the combination of Corticotropin and Roflumilast.	Asthma [CA23]	[18]
Vilanterol	DMF5EK1	Minor	Increased risk of hypokalemia by the combination of Corticotropin and Vilanterol.	Chronic obstructive pulmonary disease [CA22]	[16]
Indacaterol	DMQJHR7	Minor	Increased risk of hypokalemia by the combination of Corticotropin and Indacaterol.	Chronic obstructive pulmonary disease [CA22]	[17]
Teriflunomide	DMQ2FKJ	Major	Additive immunosuppressive effects by the combination of Corticotropin and Teriflunomide.	Hyper-lipoproteinaemia [5C80]	[19]
Amobarbital	DM0GQ8N	Moderate	Increased metabolism of Corticotropin caused by Amobarbital mediated induction of CYP450 enzyme.	Insomnia [7A00-7A0Z]	[20]
Denosumab	DMNI0KO	Moderate	Additive immunosuppressive effects by the combination of Corticotropin and Denosumab.	Low bone mass disorder [FB83]	[21]
Tecfidera	DM2OVDT	Moderate	Additive immunosuppressive effects by the combination of Corticotropin and Tecfidera.	Multiple sclerosis [8A40]	[22]
Siponimod	DM2R86O	Major	Additive immunosuppressive effects by the combination of Corticotropin and Siponimod.	Multiple sclerosis [8A40]	[16]
Fingolimod	DM5JVAN	Major	Additive immunosuppressive effects by the combination of Corticotropin and Fingolimod.	Multiple sclerosis [8A40]	[23]
Ocrelizumab	DMEZ2KH	Moderate	Additive immunosuppressive effects by the combination of Corticotropin and Ocrelizumab.	Multiple sclerosis [8A40]	[24]
Ozanimod	DMT6AM2	Major	Additive immunosuppressive effects by the combination of Corticotropin and Ozanimod.	Multiple sclerosis [8A40]	[18]
Omacetaxine mepesuccinate	DMPU2WX	Moderate	Additive immunosuppressive effects by the combination of Corticotropin and Omacetaxine mepesuccinate.	Myeloproliferative neoplasm [2A20]	[25]
Canakinumab	DM8HLO5	Moderate	Additive immunosuppressive effects by the combination of Corticotropin and Canakinumab.	Rheumatoid arthritis [FA20]	[26]
Rilonacept	DMGLUQS	Moderate	Additive immunosuppressive effects by the combination of Corticotropin and Rilonacept.	Rheumatoid arthritis [FA20]	[26]
Golimumab	DMHZV7X	Major	Additive immunosuppressive effects by the combination of Corticotropin and Golimumab.	Rheumatoid arthritis [FA20]	[27]
Anthrax vaccine	DM9GSWY	Moderate	Antagonize the effect of Corticotropin when combined with Anthrax vaccine.	Sepsis [1G40-1G41]	[28]

References

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• [18] Cerner Multum, Inc. "UK Summary of Product Characteristics.".
• [19] Product Information. Arava (leflunomide). Hoechst Marion-Roussel Inc, Kansas City, MO.
• [20] Bartoszek M, Brenner AM, Szefler SJ "Prednisolone and methylprednisolone kinetics in children receiving anticonvulsant therapy." Clin Pharmacol Ther 42 (1987): 424-32. [PMID: 3665340]
• [21] Product Information. Prolia (denosumab). Amgen USA, Thousand Oaks, CA.
• [22] Product Information. Vumerity (diroximel fumarate). Alkermes, Inc, Cambridge, MA.
• [23] Product Information. Gilenya (fingolimod). Novartis Pharmaceuticals, East Hanover, NJ.
• [24] Product Information. Ocrevus (ocrelizumab). Genentech, South San Francisco, CA.
• [25] Product Information. Synribo (omacetaxine). Teva Pharmaceuticals USA, North Wales, PA.
• [26] Product Information. Arcalyst (rilonacept). Regeneron Pharmaceuticals Inc, Tarrytown, NY.
• [27] Product Information. Cimzia (certolizumab). UCB Pharma Inc, Smyrna, GA.
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