Gusperimus is an

immunosuppressive drug Immunosuppressive drugs, also known as immunosuppressive agents, immunosuppressants and antirejection medications, are drugs that inhibit or prevent the activity of the immune system. Classification Immunosuppressive drugs can be classifie ...

. It is a derivative of the naturally occurring

HSP70 The 70 kilodalton heat shock proteins (Hsp70s or DnaK) are a family of conserved ubiquitously expressed heat shock proteins. Proteins with similar structure exist in virtually all living organisms and play crucial roles in the development of can ...

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 by

Bristol-Myers Squibb The Bristol-Myers Squibb Company, doing business as Bristol Myers Squibb (BMS), is an American multinational pharmaceutical company. Headquartered in Princeton, New Jersey, BMS is one of the world's largest pharmaceutical companies and consist ...

. Currently, it is manufactured and sponsored for use as an

orphan drug An orphan drug is a medication, pharmaceutical agent that is developed to treat certain rare medical conditions. An orphan drug would not be profitable to produce without government assistance, due to the small population of patients affected by th ...

and for clinical studies by the Japanese company Euro Nippon 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 the

pharmacokinetic Pharmacokinetics (from Ancient Greek ''pharmakon'' "drug" and ''kinetikos'' "moving, putting in motion"; see chemical kinetics), sometimes abbreviated as PK, is a branch of pharmacology dedicated to describing how the body affects a specific subs ...

properties of gusperimus.

Overview

The

European Commission The European Commission (EC) is the primary Executive (government), executive arm of the European Union (EU). It operates as a cabinet government, with a number of European Commissioner, members of the Commission (directorial system, informall ...

assigned

status to Gusperimus in 2001 for the treatment of

granulomatosis with polyangiitis Granulomatosis with polyangiitis (GPA), formerly known as Wegener's granulomatosis (WG), after Nazi German physician Friedrich Wegener, is a rare, long-term, systemic disorder that involves the formation of granulomas and vasculitis, inflammatio ...

, a serious form of

vasculitis Vasculitis is a group of disorders that destroy blood vessels by inflammation. Both artery, arteries and veins are affected. Lymphangitis (inflammation of lymphatic vessels) is sometimes considered a type of vasculitis. Vasculitis is primarily c ...

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 disease

amyotrophic lateral sclerosis Amyotrophic lateral sclerosis (ALS), also known as motor neuron disease (MND) or—in the United States—Lou Gehrig's disease (LGD), is a rare, Terminal illness, terminal neurodegenerative disease, neurodegenerative disorder that results i ...

(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 with

multiple sclerosis Multiple sclerosis (MS) is an autoimmune disease resulting in damage to myelinthe insulating covers of nerve cellsin the brain and spinal cord. As a demyelinating disease, MS disrupts the nervous system's ability to Action potential, transmit ...

. As with ALS, there are no sufficient studies in MS patients. Gusperimus may possibly be of use in more common diseases and conditions such as

rheumatoid arthritis Rheumatoid arthritis (RA) is a long-term autoimmune disorder that primarily affects synovial joint, joints. It typically results in warm, swollen, and painful joints. Pain and stiffness often worsen following rest. Most commonly, the wrist and h ...

Crohn's disease Crohn's disease is a type of inflammatory bowel disease (IBD) that may affect any segment of the gastrointestinal tract. Symptoms often include abdominal pain, diarrhea, fever, abdominal distension, and weight loss. Complications outside of the ...

lupus erythematosus is a collection of autoimmune diseases in which the human immune system becomes hyperactive and attacks healthy tissues. Symptoms of these diseases can affect many different body systems, including joints, skin, kidneys, blood cells, heart, ...

, and the prevention and therapy of

transplant rejection Transplant rejection occurs when transplanted tissue is rejected by the recipient's immune system, which destroys the transplanted tissue. Transplant rejection can be lessened by determining the molecular similitude between donor and recipien ...

graft-versus-host disease Graft-versus-host disease (GvHD) is a syndrome, characterized by inflammation in different organs. GvHD is commonly associated with bone marrow transplants and stem cell transplants. White blood cells of the donor's immune system which rema ...

Adverse effects

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

Dysgeusia Dysgeusia, also known as parageusia, is a distortion of the sense of taste. Dysgeusia is also often associated with ageusia, which is the complete lack of taste, and hypogeusia, which is a decrease in taste sensitivity. An alteration in taste or ...

(abnormal or bad taste) * Drug induced

leukopenia Leukopenia () is a decrease in the number of white blood cells (leukocytes). It places individuals at increased risk of infection as white blood cells are the body's primary defense against infections. Signs and symptoms Symptoms may include: * s ...

(very common) * 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 as

ciclosporin Ciclosporin, also spelled cyclosporine and cyclosporin, is a calcineurin inhibitor, used as an immunosuppressant medication. It is taken Oral administration, orally or intravenously for rheumatoid arthritis, psoriasis, Crohn's disease, nephr ...

tacrolimus Tacrolimus, sold under the brand name Prograf among others, is an immunosuppressive drug. After Allotransplantation, allogenic organ transplant, the risk of organ Transplant rejection, rejection is moderate. To lower the risk of organ rejectio ...

Interactions

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 serious

bone marrow Bone marrow is a semi-solid biological tissue, tissue found within the Spongy bone, spongy (also known as cancellous) portions of bones. In birds and mammals, bone marrow is the primary site of new blood cell production (or haematopoiesis). It i ...

damage increased. * Certain

NSAID Non-steroidal anti-inflammatory drugs (NSAID) are members of a therapeutic drug class which reduces pain, decreases inflammation, decreases fever, and prevents blood clots. Side effects depend on the specific drug, its dose and duration of ...

s : Increased risk of hepatotoxic reactions.

Dosage

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.

Synonyms

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- -4-[(3-aminopropyl)aminoutyl">4-[(3-aminopropyl)amino.html" ;"title="-4-[(3-aminopropyl)amino">-4-[(3-aminopropyl)aminoutylmino-
1-hydroxy-2-oxoethyl]heptanamide, * Gusperimus (Trihydrochloride), * N-[4-[(3-Aminopropyl)amino]-butyl]carbamoyl]hydroxymethyl-
7-guanidinoheptanamide, * Spanidin

Synthesis

*The BOC derivative of 4-aminobutanol is oxidized with

Collins reagent Collins reagent is the complex of chromium(VI) oxide with pyridine in dichloromethane. This metal-pyridine complex, a red solid, is used to oxidize primary alcohols to the corresponding aldehydes and secondary alcohols to the corresponding ...

to afford the aldehyde. *Condensation with the

ylide An ylide () or ylid () is a neutral dipolar molecule containing a formally negatively charged atom (usually a carbanion) directly attached to a heteroatom with a formal positive charge (usually nitrogen, phosphorus or sulfur), and in which both ...

obtained from reaction of 3-triphenylphosphonium propionic acid with lithium 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 the

amidine Amidines are organic compounds with the functional group RC(NR)NR2, where the R groups can be the same or different. They are the imine derivatives of amides (RC(O)NR2). The simplest amidine is formamidine, HC(=NH)NH2. Examples of amidines includ ...

function and formation of the corresponding

guanidine Guanidine is the compound with the formula HNC(NH2)2. It is a colourless solid that dissolves in polar solvents. It is a strong base that is used in the production of plastics and explosives. It is found in urine predominantly in patients experi ...

. *The saturated guanidino-amide is obtained by catalytic hydrogenation. Amides are well known to participate in the formation of carbinolamines and aminals. *Reaction with the glyoxilamide from

spermidine Spermidine is a polyamine compound () found in ribosomes and living tissues and having various metabolic functions within organisms. Function Spermidine is an Aliphatic compound, aliphatic polyamine. Spermidine synthase (SPDS) catalyzes its form ...

(shown as its hydrate) leads to displacement of one of the hydroxyl groups and formation of the corresponding carbinolamine, gusperimus.

References

* 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 * {{immunosuppressants Orphan drugs Guanidines Immunosuppressants