Enloplatin

Enloplatin
Clinical data
Other names	Enloplatine, enloplatino, enloplatinum
Pharmacokinetic data
Bioavailability	100% (IV)
Protein binding	> 85%
Elimination half-life	56±40 hours (Whole blood); 52±40 hours (Blood plasma)
Excretion	Renal
Identifiers
	IUPAC name [4-(azanidylmethyl)oxan-4-yl]methylazanide;cyclobutane-1,1-dicarboxylate;platinum(4+);
CAS Number	111523-41-2 ;
PubChem CID	56840924;
ChemSpider	61983;
UNII	C7HT2IO79H;
CompTox Dashboard (EPA)	DTXSID80912197 ;
Chemical and physical data
Formula	C13H20N2O5Pt
Molar mass	479.396 g·mol−1
3D model (JSmol)	Interactive image;
Melting point	260 to 263 °C (500 to 505 °F)
Solubility in water	450 mg/mL (20 °C)
	SMILES C1CC(C1)(C(=O)[O-])C(=O)[O-].C1COCCC1(C[NH-])C[NH-].[Pt+4];
	InChI InChI=1S/C7H14N2O.C6H8O4.Pt/c8-5-7(6-9)1-3-10-4-2-7;7-4(8)6(5(9)10)2-1-3-6;/h8-9H,1-6H2;1-3H2,(H,7,8)(H,9,10);/q-2;;+4/p-2; Key:NAFFDQVVNWTDJD-UHFFFAOYSA-L;

Enloplatin is a water-soluble cancer medication. It is a platinum-based antineoplastic investigated for treatment of platinum-refractory ovarian cancer, in which it was demonstrated to have minimal activity.^[3] This cancer is suspected to be at least partially cross-resistant with another third-generation platinum analog, zeniplatin, which also shows minimal antitumor activity in this type of cancer. It was found to be cross-resistant with carboplatin.^[1]

Like zeniplatin and carboplatin, use of enloplatin causes manageable nephrotoxicity, no significant neurotoxicity or ototoxicity, and dose-limiting myelosuppression.^[1]

The drug was original developed by Wyeth, but no further development since 2000 has been reported.^[4]

Structure

Like any platinum-based antineoplastic drug enloplatin is a coordination complex of platinum. Its two bidentate ligands are a tetrahydropyran-containing amine and cyclobutane dicarboxylic acid (CBDCA). Its CBDCA ligand is identical to that of carboplatin. It was found to have similar pharmokinetics to carboplatin, indicating it is the CBDCA ligand and not the amine that most influences plasma pharmokinetics of these platinum complexes.^[1]

Notes

^ As hydrate.

References

^ ^a ^b ^c ^d Kudelka AP, Siddik ZH, Tresukosol D, Edwards CL, Freedman RS, Madden TL, et al. (August 1997). "A phase II and pharmacokinetic study of enloplatin in patients with platinum refractory advanced ovarian carcinoma". Anti-Cancer Drugs. 8 (7). Ovid Technologies (Wolters Kluwer Health): 649–656. doi:10.1097/00001813-199708000-00001. PMID 9311439. S2CID 46635787.
^ Bitha P, Carvajal SG, Citarella RV, Child RG, Delos Santos EF, Dunne TS, et al. (August 1989). "Water-soluble third generation antitumor platinum complexes, [2,2-bis (aminomethyl)-1,3-propanediol-N,N']-[1,1-cyclobutanedicarboxylato (2-)-O,O']platinum(II) and [1,1-cyclobutanedicarboxylato(2-)-O,O'] [tetrahydro-4H-pyran-4,4-dimethanamine-N,N']platinum(II)". Journal of Medicinal Chemistry. 32 (8). American Chemical Society (ACS): 2015–2020. doi:10.1021/jm00128a052. PMID 2754720.
^ Amorusi P, Lessard D, Bansal SK, Selinger K, Yacobi A, Tonelli AP (August 1994). "Analysis of enloplatin by liquid chromatography and of platinum by atomic absorption spectrometry in various biological fluids". Journal of Pharmaceutical and Biomedical Analysis. 12 (8). Elsevier BV: 1023–1033. doi:10.1016/0731-7085(94)e0035-y. PMID 7819376.
^ "Enloplatin". AdisInsight. Springer Nature Switzerland AG.

[3] As hydrate.

[Kudelka_Siddik_Tresukosol_Edwards_1997_pp._649–656-1] Kudelka AP, Siddik ZH, Tresukosol D, Edwards CL, Freedman RS, Madden TL, et al. (August 1997). "A phase II and pharmacokinetic study of enloplatin in patients with platinum refractory advanced ovarian carcinoma". Anti-Cancer Drugs. 8 (7). Ovid Technologies (Wolters Kluwer Health): 649–656. doi:10.1097/00001813-199708000-00001. PMID 9311439. S2CID 46635787.

[Bitha_Carvajal_Citarella_Child_1989_pp._2015–2020-2] Bitha P, Carvajal SG, Citarella RV, Child RG, Delos Santos EF, Dunne TS, et al. (August 1989). "Water-soluble third generation antitumor platinum complexes, [2,2-bis (aminomethyl)-1,3-propanediol-N,N']-[1,1-cyclobutanedicarboxylato (2-)-O,O']platinum(II) and [1,1-cyclobutanedicarboxylato(2-)-O,O'] [tetrahydro-4H-pyran-4,4-dimethanamine-N,N']platinum(II)". Journal of Medicinal Chemistry. 32 (8). American Chemical Society (ACS): 2015–2020. doi:10.1021/jm00128a052. PMID 2754720.

[Amorusi_Lessard_Bansal_Selinger_1994_pp._1023–1033-4] Amorusi P, Lessard D, Bansal SK, Selinger K, Yacobi A, Tonelli AP (August 1994). "Analysis of enloplatin by liquid chromatography and of platinum by atomic absorption spectrometry in various biological fluids". Journal of Pharmaceutical and Biomedical Analysis. 12 (8). Elsevier BV: 1023–1033. doi:10.1016/0731-7085(94)e0035-y. PMID 7819376.

[5] "Enloplatin". AdisInsight. Springer Nature Switzerland AG.

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