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Developing specialized cancer, CNS and infectious disease pharmaceutical products

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Triapine® (CAS: 236392-56-6)

Ribonucleotide Reductase Inhibitor

cGMP API - Type II DMF (US and Canada)

IV Product -Type II DMF (US and Canada), Phase 3 clinical studies (NCI)

Oral Capsule - Type II DMF, Phase 1 clinical study (NCI)

 

Triapine® is s synthetic heterocyclic carboxaldehyde thiosemicarbazone with potential antineoplastic activity being studied in the treatment of cancer. It is a type of ribonucleotide reductase inhibitor. Also called 3-aminopyridine-2-carboxaldehyde thiosemicarbazone and 3-AP, Triapine® inhibits the enzyme ribonucleotide reductase, resulting in the inhibition of the conversion of ribonucleoside diphosphates to deoxyribonucleotides necessary for DNA synthesis. Triapine® has been tested in over 30 phase 1 and 2 clinical studies.


 
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Cloretazine (CAS: 173424-77-6)

Alkylating Agent

cGMP API - Type II DMF in preparation

IV - Phase 2 clinical program

 

Cloretazine is a sulfonyl hydrazine prodrug with antineoplastic activity being studied in the treatment of cancer. Also known as Laromustine, Onrigin, VNP40101M, or 1,2-bis(methylsulfonyl)-1-(2-chloroethyl)-2-(methylaminocarbonyl)hydrazine, Cloretazine releases the DNA chloroethylating agent 90CE after entering the blood stream. 90CE chloroethylates alkylates the 06 position of guanine, resulting in DNA crosslinking, strand breaks, chromosomal aberrations, and disruption of DNA synthesis. Intracellular metabolism of this agent also releases methyl isocyanate which inhibits 06-alkyl-guanine transferase, an enzyme involved with DNA repair. Cloretazine has been tested in over 15 phase 1 and, 2 clinical studies, as well as a single-arm phase 3 clinical study for AML.


 
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Z-Endoxifen (CAS: 1032008-74-4)

Selective Estrogen Receptor Modulator (SERM) 

cGMP API - Type II DMF in preparation

Oral Product - Phase 1 clinical study (partner)

 

Z-endoxifen is the z (cis-) stereoisomer of endoxifen with potential antineoplastic activity. Endoxifen, also known as N-desmethyl-4-hydroxytamoxifen, is under development for estrogen receptor-positive breast cancer. Endoxifen is a nonsteroidal selective estrogen receptor modulator (SERM) of the triphenylethylene group. Endoxifen competitively inhibits the binding of estradiol to estrogen receptors, thereby preventing the receptor from binding to the estrogen-response element on DNA and thus reducing DNA synthesis. It is an active metabolite of tamoxifen and has been found to be effective in patients that have failed previous hormonal therapies (tamoxifen, aromatase inhibitors, and fulvestrant). The prodrug tamoxifen is metabolized by the CYP2D6 enzyme to produce afimoxifene (4-hydroxytamoxifen) and endoxifen. Unlike tamoxifen, however, which relies on CYP2D6 activity for its conversion to the active metabolite endoxifen, the direct administration of endoxifen bypasses the CYP2D6 route. As CYP2D6 activity can vary widely among individuals due to genetic CYP2D6 polymorphisms, endoxifen is therefore theoretically more potent and more uniform in its bioavailability across patient populations. Nanopharmaceutics is supporting the CMC package for a partner and a Type II DMF is in preparation for submission to the FDA.