Delving into the Latest Updates on Canfosfamide Hydrochloride with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Canfosfamide, Canfosfamide hydrochloride (USAN), TER 286

+ [4]

Target

DNA

Action

inhibitors

Mechanism

DNA inhibitors(DNA inhibitors), DNA alkylating agents

Therapeutic Areas

NeoplasmsEndocrinology and Metabolic DiseaseRespiratory Diseases+ [4]

Active Indication-

Inactive Indication

Advanced Lung Non-Small Cell CarcinomaCarcinomaMetastatic breast cancer+ [6]

Originator Organization

MabVax Therapeutics, Inc.

Active Organization-

Inactive Organization

Telik, Inc.

MabVax Therapeutics Holdings, Inc.

Taiho Pharmaceutical Co., Ltd.

Drug Highest PhaseDiscontinuedPhase 3

First Approval Date-

Regulation-

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Structure/Sequence

Molecular FormulaC26H41Cl5N5O10PS

InChIKeyNECZZOFFLFZNHL-XVGZVFJZSA-N

CAS Registry439943-59-6

This is a Phase 2 study to determine the efficacy and safety of canfosfamide treatment in relapsed or refractory mantle cell lymphoma, diffuse large B cell lymphoma and multiple myeloma. The study will be conducted in two stages with 5-6 patients in each indication in Stage 1 and if responses are observed an additional 10 patients in Stage 2 in each group.

Start Date01 Jun 2010

Sponsor / Collaborator

Telik, Inc.

NCT00350948

/ TerminatedPhase 3

Phase 3 Randomized Study of TLK286 (Telcyta®) in Combination With Liposomal Doxorubicin (Doxil/Caelyx)Versus Liposomal Doxorubicin (Doxil/Caelyx) as Second-Line Therapy in Platinum Refractory or Resistant Ovarian Cancer (ASSIST-5)

The purpose of this research study is to determine if Telcyta® given in combination with liposomal doxorubicin is more effective than liposomal doxorubicin alone in treating women who have recurrent ovarian epithelial cancer, fallopian tube cancer or primary peritoneal cancer that is refractory or resistant to platinum chemotherapy.

Start Date01 May 2006

Sponsor / Collaborator

Telik, Inc.

NCT00102973

/ CompletedPhase 3

Phase III Randomized Study of TLK286 (Telcyta) in Combination With Carboplatin (Paraplatin) Versus Liposomal Doxorubicin (Doxil) as Second-Line Therapy in Platinum Refractory or Resistant Ovarian Cancer [ASSIST-3]

The purpose of this research study is to determine if TLK286 given in combination with carboplatin is more effective than liposomal doxorubicin in treating women who have recurrent ovarian epithelial cancer, fallopian tube cancer, or primary peritoneal cancer, that is refractory or resistant to platinum chemotherapy.

Start Date01 Dec 2004

Sponsor / Collaborator

Telik, Inc.

100 Clinical Results associated with Canfosfamide Hydrochloride

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100 Translational Medicine associated with Canfosfamide Hydrochloride

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100 Patents (Medical) associated with Canfosfamide Hydrochloride

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46

Literatures (Medical) associated with Canfosfamide Hydrochloride

08 Mar 2018·Journal of medicinal chemistryQ1 · MEDICINE

Glutathione S-Transferase π-Activatable O²-(Sulfonylethyl Derived) Diazeniumdiolates Potently Suppress Melanoma in Vitro and in Vivo

Q1 · MEDICINE

Article

Author: Kaur, Jatinder ; Zhang, Yinqiu ; Yuan, Haoliang ; Zou, Yu ; Wu, Jianbing ; Huang, Zhangjian ; Fei, Yue ; Zhang, Yihua ; Bhardwaj, Atul ; Knaus, Edward E.

A group of glutathione S-transferase π (GSTπ) activatable O²-(sulfonylethyl derived) diazeniumdiolates 5-12 were designed and synthesized. These compounds could be activated by GSTπ to initiate the β-elimination reaction, liberating an active vinyl sulfone-based GSH derivative and a diazeniumdiolate anion which subsequently releases NO in situ. The most active compound 6 released relatively high levels of NO and inhibited proliferation of melanoma B16 cells, superior to a diazeniumdiolate-based anticancer agent JS-K (1). Importantly, 6 had 8-fold less inhibitory activity against normal epithelial JB6 Cl 30-7b cells. The inhibitory activity of 6 could be diminished by an NO scavenger or GSTπ inhibitor. Furthermore, 6 induced nitration of mitochondrial tyrosine in B16 cells and inoculated B16 tumors in mice, which might be responsible for oxidation of protein leading to tumor suppression. Finally, 6 significantly retarded the B16 cells growth in a mouse xenograft model. These findings suggest that 6 may have a potential to treat melanoma.

12 Nov 2013·BiochemistryQ3 · BIOLOGY

Mechanism of Glutathione Transferase P1-1-Catalyzed Activation of the Prodrug Canfosfamide (TLK286, TELCYTA)

Q3 · BIOLOGY

Article

Author: Fernandes, Pedro Alexandrino ; Ramos, Maria João ; Mannervik, Bengt ; Dourado, Daniel F. A. R.

Canfosfamide (TLK286, TELCYTA) is a prodrug that upon activation by glutathione transferase P1-1 (GST P1-1) yields an anticancer alkylating agent and a glutathione derivative. The rationale underlying the use of TLK286 in chemotherapy is that tumor cells overexpressing GST P1-1 will be locally exposed to the released alkylating agent with limited collateral toxicity to the surrounding normal tissues. TLK286 has demonstrated clinical effects in phase II and III clinical trials for the treatment of malignancies, such as ovarian cancer, nonsmall cell lung cancer, and breast cancer, as a single agent and in combination with other chemotherapeutic agents. In spite of these promising results, the detailed mechanism of GST P1-1 activation of the prodrug has not been elucidated. Here, we propose a mechanism for the TLK286 activation by GST P1-1 on the basis of density functional theory (DFT) and on potential of mean force (PMF) calculations. A catalytic water molecule is instrumental to the activation by forming a network of intermolecular interactions between the active-site Tyr7 hydroxyl and the sulfone and COO(-) groups of TLK286. The results obtained are consistent with the available experimental kinetic data and provide an atomistic understanding of the TLK286 activation mechanism.

01 Sep 2013·The oncologistQ2 · MEDICINE

The Role of Pegylated Liposomal Doxorubicin in Ovarian Cancer: A Meta-Analysis of Randomized Clinical Trials

Q2 · MEDICINE

Article

Author: La-Beck, Ninh M. ; Alzghari, Saeed ; Gibson, Jean-Marie ; Trantham, Holly ; Ahn, Chul

Learning Objectives:

Determine circumstances under which ovarian cancer patients would benefit from carboplatin plus pegylated liposomal doxorubicin rather than carboplatin plus paclitaxel. Compare and contrast efficacy and toxicity profiles of carboplatin plus pegylated liposomal doxorubicin versus carboplatin plus paclitaxel. Compare and contrast efficacy and toxicity profiles of single agent pegylated liposomal doxorubicin versus topotecan, gemcitabine, olaparib, patupilone, and canfosfamide.

1

News (Medical) associated with Canfosfamide Hydrochloride

02 Aug 2007

·www.biospace.com

Telik, Inc. Announces 2007 Second Quarter Financial Release, Conference Call and Webcast

PALO ALTO, Calif., Aug. 1 /PRNewswire-FirstCall/ -- Telik, Inc. announced that its 2007 second quarter conference call and webcast will be held on Wednesday, August 8, 2007 at 4:30 p.m. Eastern time (1:30 p.m. Pacific time) following the release earlier that day of the company's financial results for the second quarter and six months ended June 30, 2007. The conference call will be accessible via Telik's website at or by telephone at 888-428-4473 or 612-332-0107. An archive of the conference call will be available on the Telik website or by telephone at 800-475-6701 or 320-365-3844, access code 882545. The archive will be available from approximately 8:30 p.m. Eastern time on August 8 through August 15, 2007. Telik, Inc. of Palo Alto, CA is a biopharmaceutical company focused on discovering, developing and commercializing novel small molecule drugs to treat serious diseases. The company's most advanced drug development candidate is TELCYTA, a tumor-activated small molecule product candidate in clinical development for the treatment of advanced ovarian cancer and non-small cell lung cancer. A second drug development candidate, TELINTRA(TM), is in clinical development for myelodysplastic syndrome. Telik's product candidates were discovered using its proprietary drug discovery technology, TRAP(TM), which enables the rapid and efficient discovery of small molecule drug candidates. Additional information is available at . Telik, Inc. CONTACT: Carol D. DeGuzman, Senior Director, Corporate Communications ofTelik, Inc., +1-650-845-7728, cdeguzman@telik.com Web site:

Financial StatementSmall molecular drug

100 Deals associated with Canfosfamide Hydrochloride

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External Link

KEGG	Wiki	ATC	Drug Bank
D03351	-	-	DB04972

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Non-Small Cell Lung Cancer	Phase 3	Argentina	Telik, Inc.	26 Mar 2004
Non-Small Cell Lung Cancer	Phase 3	Australia	Telik, Inc.	26 Mar 2004
Non-Small Cell Lung Cancer	Phase 3	Brazil	Telik, Inc.	26 Mar 2004
Non-Small Cell Lung Cancer	Phase 3	Chile	Telik, Inc.	26 Mar 2004
Non-Small Cell Lung Cancer	Phase 3	Germany	Telik, Inc.	26 Mar 2004
Non-Small Cell Lung Cancer	Phase 3	Italy	Telik, Inc.	26 Mar 2004
Non-Small Cell Lung Cancer	Phase 3	United Kingdom	Telik, Inc.	26 Mar 2004
Platinum-Resistant Ovarian Carcinoma	Phase 3	United States	Telik, Inc.	01 Jun 2003
Platinum-Resistant Ovarian Carcinoma	Phase 3	Argentina	Telik, Inc.	01 Jun 2003
Platinum-Resistant Ovarian Carcinoma	Phase 3	Belgium	Telik, Inc.	01 Jun 2003

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT00350948 (Pubmed \| Int J Gynecol Cancer)	Phase 3	Platinum-Resistant Ovarian Carcinoma	125	Canfosfamide + PLD	mdvlgutnmh(qwzsnahjkz) = jrrnebsieb cjawwdrili (rtfupcyqzs )	Positive	01 Jul 2010
				PLD	mdvlgutnmh(qwzsnahjkz) = zbcgapwuhp cjawwdrili (rtfupcyqzs )
NCT00052065 (Pubmed \| J Hematol Oncol)	Phase 2	Platinum-Resistant Epithelial Ovarian Carcinoma	-	Canfosfamide	xbjmlnexru(vadijdsiky) = twmyeuunhx euwmwxrttu (iatfvuamww, 14.2 - 45.2) View more	-	11 Mar 2010
ASCO2009	Phase 3	Refractory Ovarian Carcinoma \| Platinum-Resistant Ovarian Carcinoma Second line	244	Canfosfamide (C) plus pegylated liposomal doxorubicin (PLD)	lxekxcnist(pjakflrdpg) = zldtkwwnft mgckhczwox (sygvuynhrq ) View more	-	20 May 2009
				PLD	lxekxcnist(pjakflrdpg) = vjslmiugtx mgckhczwox (sygvuynhrq ) View more
ASCO2007	Phase 3	Platinum-Resistant Ovarian Carcinoma	461	Canfosfamide (C)	kbsijziees(iuvbystnwd) = psoocqxjze yslvmypuyq (fgyfaccujr ) View more	-	20 Jun 2007
				Pegylated liposomal doxorubicin (D)	kbsijziees(iuvbystnwd) = ymgpqragjy yslvmypuyq (fgyfaccujr ) View more
ASCO2007	Phase 3	Platinum-Resistant Ovarian Carcinoma	247	Canfosfamide (C) plus carboplatin (P)	zqvhxljhmp(itiypjhnbr) = lsqdmcfcns sxmzlbdtfk (lzslcdfdmz )	-	20 Jun 2007
				liposomal doxorubicin (D)	zqvhxljhmp(itiypjhnbr) = jttkonxsdr sxmzlbdtfk (lzslcdfdmz )
Pubmed \| Int J Gynecol Cancer	Phase 2	Platinum-Resistant Ovarian Carcinoma	-	TLK286 (TELCYTA)	ibrrtxrqkg(qbkitkjnoz) = dcpwnwjuas ajkfjaamsa (jwcbaqkdhl ) View more	-	01 Jul 2005
ASCO2004	Phase 1/2	Platinum-Resistant Ovarian Carcinoma	-	TLK286	yxnsmezgbw(txhlamyfst) = 5 pts saxucqghjv (cpuvhfccyu ) View more	-	15 Jul 2004
				Carboplatin
ASCO2004	Phase 1/2	Platinum-Resistant Ovarian Carcinoma	17	TLK286	qdbkszpgzs(jrkgodijsj) = xgihavorbn ocwheqlqdh (xhtcliracc ) View more	-	15 Jul 2004
				Doxil	ghvkxwwigf(hkfczmvfnh) = rcvizqaupt awvocgoykp (myiuwkmzws )
ASCO2004	Phase 1/2	Non-Small Cell Lung Cancer	30	TLK286	sckgfldhwr(isyglwfifd) = napmsmebig ntbuacofyi (cbkbsppmce ) View more	-	15 Jul 2004
				Docetaxel	sckgfldhwr(isyglwfifd) = spntsnhjlx ntbuacofyi (cbkbsppmce )