Gusperimus

Names
Other names N-[2-[4-(3-Aminopropylamino)butylamino]-1-hydroxy-2-oxoethyl]-7-(diaminomethylideneamino)heptanamide[1]
Identifiers
CAS Number	98629-43-7 N
3D model (JSmol)	Interactive image
ChEMBL	ChEMBL406117 Y ChEMBL1172736 Y
ChemSpider	49995 Y 82420 S Y
KEGG	D08032 Y
MeSH	gusperimus
PubChemCID	55362 91272 S
UNII	UJ0ZJ76DO9 Y
CompTox Dashboard(EPA)	DTXSID60861078
InChI InChI=1S/C17H37N7O3/c18-9-7-11-21-10-5-6-12-22-15(26)16(27)24-14(25)8-3-1-2-4-13-23-17(19)20/h16,21,27H,1-13,18H2,(H,22,26)(H,24,25)(H4,19,20,23) Y Key: IDINUJSAMVOPCM-UHFFFAOYSA-N Y
SMILES N=C(N)NCCCCCCC(=O)NC(O)C(=O)NCCCCNCCCN
Properties
Chemical formula	C17H37N7O3
Molar mass	387.529 g·mol−1
logP	−0.933
Acidity (pKa)	11.588
Basicity (pKb)	2.409
Pharmacology
ATC code	L04AA19 (WHO)
Routes of administration	Intravenous Subcutaneous
Pharmacokinetics:
Bioavailability	100%
Legal status	In general: ℞ (Prescription only)
Related compounds
Related compounds	Dibutylhexamethylenediamine Acetyl hexapeptide-3
Except where otherwise noted, data are given for materials in theirstandard state (at 25 °C [77 °F], 100 kPa). N verify (what is YN ?) Infobox references

Gusperimus is animmunosuppressive drug. It is a derivative of the naturally occurringHSP70 inhibitor spergualin, and inhibits the interleukin-2-stimulated maturation of T cells to the S and G2/M phases and the polarization of the T cells into IFN-gamma-secreting Th1 effector T cells, resulting in the inhibition of growth of activated naive CD4 T cells.

Gusperimus was developed byBristol-Myers Squibb. Currently, it is manufactured and sponsored for use as anorphan drug and for clinical studies by the Japanese company EuroNippon Kayaku. The patent claim (see quotation) is that Gusperimus may be useful for a variety of hyperreactive inflammatory diseases such as autoimmune diseases. The drug is available in vials containing 100 mg each.

There is little information about thepharmacokinetic properties of gusperimus.

TheEuropean Commission assignedorphan drug status to Gusperimus in 2001 for the treatment ofgranulomatosis with polyangiitis, a serious form ofvasculitis frequently associated with permanent disability and/or fatal outcome. There have been many cases of patients resistant to all forms of usual treatment responding very well to Gusperimus.

It has been proposed that gusperimus may benefit patients with the neurological diseaseamyotrophic lateral sclerosis (ALS or Lou Gehrig's disease). ALS causes permanent motor deficits and disabilities up to the point that almost all motor functions, including breathing and bladder control, are lost. Patients usually have no intellectual impairments. Currently, there are no results from controlled studies in ALS patients.

There have also been positive and negative anecdotal reports in patients withmultiple sclerosis. As with ALS, there are no sufficient studies in MS patients.

Gusperimus may possibly be of use in more common diseases and conditions such asrheumatoid arthritis,Crohn's disease,lupus erythematosus, and the prevention and therapy oftransplant rejection orgraft-versus-host disease.

Currently, only provisional and preliminary data about side-effects is available. The following side-effects have been noticed so far:

• Dysgeusia (abnormal or bad taste)
• Drug inducedleukopenia (very common)^[quantify]
• Significant infections related to therapy.

It is not known if therapy with gusperimus may increase the risk of malignant diseases (lymphoma, leukemia, solid tumors), as is the case with other highly potent immunosuppressant agents such asciclosporin ortacrolimus.

There has been little experience about clinically relevant interactions. These might be:

• Other immunosuppressant drugs : Risk of infections increased.
• Myelotoxic drugs like 6-Mercaptopurin : Risk of seriousbone marrow damage increased.
• CertainNSAIDs : Increased risk of hepatotoxic reactions.

Gusperimus is used in therapeutic cycles. The daily dose and the length of each cycle as well as the length of the treatment free interval depend on the degree of leukopenia/neutropenia caused by gusperimus. It is recommended to obtain complete WBC (White Blood Cell) counts during and after each cycle frequently.

2Common references are:

• (+−)-15-Deoxyspergualin,
• 1-Amino-19-guanidino-11-hydroxy-4,9,12-triazanonadecane-10,13-dione,
• 15-Deoxyspergualin,
• 15-Deoxyspergualin Hydrochloride,
• 7-{(Aminoiminomethyl)amino]-N-[2-[[4-[(3-aminopropyl)amino]butyl]amino]]-
  1-hydroxy-2-oxoethyl]heptanamide,
• Gusperimus (Trihydrochloride),
• N-[[[4-[(3-Aminopropyl)amino]-butyl]carbamoyl]hydroxymethyl]]-
  7-guanidinoheptanamide,
• Spanidin

• The BOC derivative of 4-aminobutanol is oxidized withCollins reagent to afford the aldehyde.
• Condensation with theylide obtained from reaction of 3-triphenylphosphonium propionic acid withlithium hexamethyldisilazane leads to the chain extended acid.
• The carboxylic acid is then activated by conversion to its N-hydroxysuccinimide ester; That group is displaced by ammonia to give the corresponding amide and the BOC group is removed by acid to give the intermediate.
• Treatment of the aminoamide with 1-amidino-3,5-dimethylpyrazole leads to an exchange of theamidine function and formation of the correspondingguanidine.
• The saturated guanidino-amide is obtained bycatalytic hydrogenation. Amides are well known to participate in the formation ofcarbinolamines andaminals.
• Reaction with theglyoxilamide fromspermidine (shown as its hydrate) leads to displacement of one of the hydroxyl groups and formation of the correspondingcarbinolamine, gusperimus.

This article includes a list ofgeneral references, butit lacks sufficient correspondinginline citations. Please help toimprove this article byintroducing more precise citations.(February 2008) (Learn how and when to remove this message)

• https://web.archive.org/web/20120204123305/http://www.bizbozos.com/nci_Gusperimus
• http://ec.europa.eu/enterprise/pharmaceuticals/register/o034.htm
• https://web.archive.org/web/20060109201017/http://www.als.net/research/treatments/treatmentDetail.asp?treatmentID=858
• "Gusperimus: Leucopenia, infection, dysgeusia: 3 case reports".Reactions Weekly.1 (1080): 13. 2005.

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• Immunosuppressants

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