| Revision as of 13:38, 27 October 2011 editBeetstra (talk | contribs)Edit filter managers, Administrators172,084 edits Script assisted update of identifiers for the Chem/Drugbox validation project (updated: 'ChEMBL', 'StdInChI', 'StdInChIKey', 'CAS_number').← Previous edit | Latest revision as of 05:37, 13 October 2023 edit undoJsjsjs1111 (talk | contribs)Extended confirmed users2,546 edits removed Category:IARC Group 1 carcinogens using HotCat | ||
| (57 intermediate revisions by 22 users not shown) | |||
| Line 1: | Line 1: | ||
| {{Short description|Chemical compound}} | |||
| {{Orphan|date=February 2011}} | |||
| {{Drugbox | {{Drugbox | ||
| | Verifiedfields = changed | |||
| ⚫ | | IUPAC_name = 2- |
||
| | verifiedrevid = 457654634 | |||
| | image = 4hydroxycyclophosphamide.png | |||
| ⚫ | | IUPAC_name = (2''S'',4''S'')-''N'',''N''-Bis(2-chloroethyl)-4-hydroperoxy-2-oxo-1,3,2λ<sup>5</sup>-oxazaphosphinan-2-amine | ||
| ⚫ | | width = |
||
| | image = 4-hydroperoxycyclophosphamide.svg | |||
| ⚫ | | width = 125 | ||
| | alt = | | alt = | ||
| | |
| drug_name = | ||
| | width2 = | |||
| | imagename = <!-- else may use drug_name --> | |||
| | drug_name = <!-- else may use imagename --> | |||
| <!--Clinical data--> | <!-- Clinical data --> | ||
| | tradename = |
| tradename = | ||
| | licence_EU = <!-- EMA requires brand name --> | |||
| | licence_US = <!-- FDA may use generic name --> | |||
| | DailyMedID = <!-- preference to licence_US --> | | DailyMedID = <!-- preference to licence_US --> | ||
| ⚫ | | legal_status = | ||
| | pregnancy_AU = <!-- A / B1 / B2 / B3 / C / D / X --> | |||
| ⚫ | | dependency_liability = | ||
| | pregnancy_US = <!-- A / B / C / D / X --> | |||
| | routes_of_administration = Extracorporal treatment of cellular masses; ] | |||
| | pregnancy_category = | |||
| | legal_AU = <!-- S2, S3, S4, S5, S6, S7, S8, S9 or Unscheduled--> | |||
| | legal_CA = <!-- OTC, Rx-only, Schedule I, II, III, IV, V, VI, VII, VIII --> | |||
| | legal_UK = <!-- GSL, P, POM, CD, CD Lic, CD POM, CD No Reg POM, CD (Benz) POM, CD (Anab) POM or CD Inv POM --> | |||
| | legal_US = <!-- OTC / Rx-only / Schedule I, II, III, IV, V --> | |||
| ⚫ | | legal_status = |
||
| ⚫ | | dependency_liability = |
||
| | routes_of_administration = | |||
| <!--Pharmacokinetic data--> | <!-- Pharmacokinetic data --> | ||
| | bioavailability = | | bioavailability = | ||
| | protein_bound = | | protein_bound = | ||
| Line 33: | Line 23: | ||
| | excretion = | | excretion = | ||
| <!--Identifiers--> | <!-- Identifiers --> | ||
| | CAS_number_Ref = {{cascite|correct}} | |||
| | CAS_number = <!-- blanked - oldvalue: 40277-05-2 --> | |||
| | CAS_number = 39800-16-3 | |||
| | UNII_Ref = {{fdacite|correct|FDA}} | |||
| | UNII = U880A4FUDA | |||
| | CAS_supplemental = | | CAS_supplemental = | ||
| | ATCvet = | | ATCvet = | ||
| | ATC_prefix = |
| ATC_prefix = L01 | ||
| | ATC_suffix = | | ATC_suffix = | ||
| | ATC_supplemental = | | ATC_supplemental = | ||
| | PubChem = | | PubChem = 38347 | ||
| | PubChemSubstance = |
| PubChemSubstance = | ||
| | IUPHAR_ligand = |
| IUPHAR_ligand = | ||
| | DrugBank_Ref = {{drugbankcite|correct|drugbank}} | |||
| | DrugBank = | |||
| | |
| DrugBank = | ||
| | ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} | |||
| | ChEMBL = <!-- blanked - oldvalue: 731 --> | |||
| | |
| ChemSpiderID = 35147 | ||
| | ChEMBL_Ref = {{ebicite|correct|EBI}} | |||
| | ChEMBL = 61511 | |||
| | ChEBI = 196991 | |||
| | ChEBI_Ref = {{ebicite|correct|EBI}} | |||
| | synonyms = Perfosfamide | |||
| <!--Chemical data--> | <!-- Chemical data --> | ||
| | C=7 | H=15 | Cl=2 | N=2 | O=4 | P=1 | |||
| | chemical_formula = | |||
| ⚫ | | smiles = C1COP(=O)(NC1OO)N(CCCl)CCCl | ||
| | C=7 | H=15 | Ag= | As= | Au= | B= | Bi= | Br= | Cl=2 | Co= | F= | Fe= | Gd= | I= | K= | Mn= | N=2 | Na= | O=3 | P=1 | Pt= | S= | C= | Se= | Sr= | Tc= | charge = | |||
| | StdInChI_Ref = {{stdinchicite|correct|chemspider}} | |||
| | molecular_weight = | |||
| ⚫ | | StdInChI = 1S/C7H15Cl2N2O4P/c8-2-4-11(5-3-9)16(13)10-7(15-12)1-6-14-16/h7,12H,1-6H2,(H,10,13)/t7-,16-/m0/s1 | ||
| ⚫ | | smiles = |
||
| | StdInChIKey_Ref = {{stdinchicite|correct|chemspider}} | |||
| ⚫ | | StdInChI = |
||
| | StdInChIKey = |
| StdInChIKey = VPAWVRUHMJVRHU-GYKQLYQFSA-N | ||
| | density = | | density = | ||
| | melting_point = | | melting_point = | ||
| Line 66: | Line 64: | ||
| }} | }} | ||
| '''Perfosfamide''', or '''4-hydroperoxycyclophosphamide''' (trade name '''Pergamid''') was an experimental drug candidate for blood cancers that was rejected by the FDA in 1993 and never reached the market. | |||
| '''4-Hydroxycyclophosphamide''' is the main, ] ] of ].<ref>{{cite journal | doi = 10.1021/ja00803a070 | last1 = Van Der Steen | first1 = J. | last2 = Timmer | first2 = E. C. | last3 = Westra | first3 = J. G. | last4 = Benckhuysen | first4 = C. | title = 4-Hydroperoxidation in the Fenton oxidation of the antitumor agent cyclophosphamide | journal = ] | volume = 95 | pages = 7535 | year = 1973}}</ref><ref>{{cite journal | doi = 10.1006/abio.1995.1021 | last1 = Wright | first1 = JE | last2 = Tretyakov | first2 = O | last3 = Ayash | first3 = LJ | last4 = Elias | first4 = A | last5 = Rosowsky | first5 = A | last6 = Frei E | first6 = 3rd | title = Analysis of 4-hydroxycyclophosphamide in human blood | journal = Analyt. Biochem. | volume = 224 | issue = 1 | pages = 154–158 | year = 1995 | pmid = 7710063}}</ref> | |||
| == |
==Intended use== | ||
| Perfosfamide was used experimentally by oncologists in the 1980s for use in ] procedures for treatment of blood cancers. It was added to the tissue after it had been taken from the donor but before the tissue was administered to the patient to "purge" ]s in order to prevent ], which results from donor lymphocytes attacking normal host cells and tissues, and to "purge" a patient's own (autologous) collected ] of any ]s it may still contain at the time of harvesting.<ref>{{cite journal | vauthors = Sládek NE | title = Aldehyde dehydrogenase-mediated cellular relative insensitivity to the oxazaphosphorines | journal = Current Pharmaceutical Design | volume = 5 | issue = 8 | pages = 607–25 | date = August 1999 | doi = 10.2174/1381612805666230110215319 | pmid = 10469894 }}</ref><ref>{{cite book | vauthors = Colvinn OM | chapter = Chapter 20: Pharmacologic Purging of Bone Marrow. | title = Thomas' Hematopoietic Cell Transplantation | volume = 457 | veditors = Thomas ED, etal | publisher = John Wiley & Sons | date = 2004 | isbn = 9781405112567 }}</ref>{{rp|255}} | |||
| In 1989 Nova Pharmaceutical took over development of the compound and in 1992, it submitted a ] to the FDA for using perfosamide to purge malignant cells in transplants for the treatment of ]. In the ensuing year, it merged with Scios to become Scios Nova. In March 1993, the FDA's Oncology Drugs Advisory Committee rejected the application because all the data was from the experimental uses, and no ] had been conducted.<ref>{{cite journal | first = Jeffrey L. | last = Fox | name-list-style = vanc | title = Scios Nova may purge Pergamid after FDA setback. | journal = Nature Biotechnology | date = April 1993 | volume = 11 | issue = 4 | pages = 439 | doi = 10.1038/nbt0493-439 | s2cid = 6110616 }}</ref> At the review meeting, Scios Nova also announced that it would not fund further development of the drug candidate.<ref>{{cite web | work = The Pink Sheet | date = 8 March 1993 | url = https://www.pharmamedtechbi.com/publications/the-pink-sheet/55/010/scios-novas-pergamid-no-further-trials-will-be-funded | title = Scios Nova's Pergamid: No Further Trials Will Be Funded }}</ref> | |||
| ==Chemistry== | |||
| Perfosfamide is an oxazaphosphorine compound, similar to ] and ]. Like those compounds it, is metabolized to ], which eventually gives rise to the two directly cytotoxic metabolites — ] and ].<ref>{{cite journal | vauthors = Ludeman SM | title = The chemistry of the metabolites of cyclophosphamide | journal = Current Pharmaceutical Design | volume = 5 | issue = 8 | pages = 627–43 | date = August 1999 | doi = 10.2174/1381612805666230110215458 | pmid = 10469895 }}</ref> | |||
| == References == | |||
| {{reflist}} | {{reflist}} | ||
| {{Chemotherapeutic agents}} | {{Chemotherapeutic agents}} | ||
| ] | |||
| {{DEFAULTSORT:Hydroxycyclophosphamide, 4-}} | |||
| ] | ] | ||
| ] | |||
| ] | |||
| ] | ] | ||
| ] | ] | ||
| ] | ] | ||
| ] | |||
| ] | |||
| ] | |||
Latest revision as of 05:37, 13 October 2023
Chemical compound Pharmaceutical compound | |
| Clinical data | |
|---|---|
| Other names | Perfosfamide |
| Routes of administration | Extracorporal treatment of cellular masses; intravenously |
| ATC code | |
| Identifiers | |
IUPAC name
| |
| CAS Number | |
| PubChem CID | |
| ChemSpider | |
| UNII | |
| ChEBI | |
| ChEMBL | |
| CompTox Dashboard (EPA) | |
| Chemical and physical data | |
| Formula | C7H15Cl2N2O4P |
| Molar mass | 293.08 g·mol |
| 3D model (JSmol) | |
SMILES
| |
InChI
| |
| (what is this?) (verify) | |
Perfosfamide, or 4-hydroperoxycyclophosphamide (trade name Pergamid) was an experimental drug candidate for blood cancers that was rejected by the FDA in 1993 and never reached the market.
Intended use
Perfosfamide was used experimentally by oncologists in the 1980s for use in bone marrow transplant procedures for treatment of blood cancers. It was added to the tissue after it had been taken from the donor but before the tissue was administered to the patient to "purge" lymphocytes in order to prevent Graft Versus Host Disease, which results from donor lymphocytes attacking normal host cells and tissues, and to "purge" a patient's own (autologous) collected hematopoietic stem cells of any malignant cells it may still contain at the time of harvesting.
In 1989 Nova Pharmaceutical took over development of the compound and in 1992, it submitted a new drug application to the FDA for using perfosamide to purge malignant cells in transplants for the treatment of acute myeloid leukemia. In the ensuing year, it merged with Scios to become Scios Nova. In March 1993, the FDA's Oncology Drugs Advisory Committee rejected the application because all the data was from the experimental uses, and no randomized clinical trial had been conducted. At the review meeting, Scios Nova also announced that it would not fund further development of the drug candidate.
Chemistry
Perfosfamide is an oxazaphosphorine compound, similar to mafosfamide and cyclophosphamide. Like those compounds it, is metabolized to 4-hydroxycyclophosphamide, which eventually gives rise to the two directly cytotoxic metabolites — phosphoramide mustard and acrolein.
References
- Sládek NE (August 1999). "Aldehyde dehydrogenase-mediated cellular relative insensitivity to the oxazaphosphorines". Current Pharmaceutical Design. 5 (8): 607–25. doi:10.2174/1381612805666230110215319. PMID 10469894.
- Colvinn OM (2004). "Chapter 20: Pharmacologic Purging of Bone Marrow.". In Thomas ED, et al. (eds.). Thomas' Hematopoietic Cell Transplantation. Vol. 457. John Wiley & Sons. ISBN 9781405112567.
- Fox JL (April 1993). "Scios Nova may purge Pergamid after FDA setback". Nature Biotechnology. 11 (4): 439. doi:10.1038/nbt0493-439. S2CID 6110616.
- "Scios Nova's Pergamid: No Further Trials Will Be Funded". The Pink Sheet. 8 March 1993.
- Ludeman SM (August 1999). "The chemistry of the metabolites of cyclophosphamide". Current Pharmaceutical Design. 5 (8): 627–43. doi:10.2174/1381612805666230110215458. PMID 10469895.