ONX 0801 (BGC 945) trisodium is a thymidylate synthase (TS) inhibitor, targeted to α-folate receptor–overexpressing tumors[1][2].
体外研究 (In Vitro)
ONX 0801 (BGC 945) is designed to further reduce toxicity by more effectively targeting cancer cells that overexpress the α-FR[1]. ONX 0801 (BGC 945) exhibits IC50 values of of 6.6 μM, 1.1 nM, 3.3 nM, 90 nM and 0.32 μM in A431, A431-FBP, KB, IGROV-1 and JEG-3 cells[2].
Shanghai Jinpan Biotech Co Ltd has not independently confirmed the accuracy of these methods. They are for reference only.
体内研究 (In Vivo)
BGC 945 (100 mg/kg, ip/iv injection) in the tumor had a longer half-life (28 hours) compared with other tissues[2]. BGC 945 (100 mg/kg daily for 16 days) does not lead to body weight loss, macroscopic signs of toxicity to the major organs, or a change in renal function[2]. BGC 945 at 100mg/kg induces a 5-20-fold increase in tumor dUrd at 4-72h without increases in the plasma, consistent with tumor targeting[2].
Shanghai Jinpan Biotech Co Ltd has not independently confirmed the accuracy of these methods. They are for reference only.
Animal Model:
Mice (on the folate-free diet for 5 days were transplanted with tumor and the implants)[2].
Dosage:
100 mg/kg (Pharmacokinetic Analysis).
Administration:
Single i.p. or iv injection.
Result:
After i.p. injection, the compound was well absorbed from the peritoneal cavity. The plasma AUC was 50% higher for i.p. compared with i.v. administration and was also higher in spleen, kidney, and liver by this route. Tumor AUC was similar via either route.
分子量
713.58
Formula
C32H30N5Na3O10
CAS 号
1097638-00-0
运输条件
Room temperature in continental US; may vary elsewhere.
储存方式
Please store the product under the recommended conditions in the Certificate of Analysis.
参考文献
[1]. Anna Tochowicz, et al. Development and binding mode assessment of N-[4-[2-propyn-1-yl[(6S)-4,6,7,8-tetrahydro-2-(hydroxymethyl)-4-oxo-3H-cyclopenta[g]quinazolin-6-yl]amino]benzoyl]-l-γ-glutamyl-D-glutamic acid (BGC 945), a novel thymidylate synthase inhibitor that targets tumor cells. J Med Chem. 2013 Jul 11;56(13):5446-55.
[2]. David D Gibbs, et al. BGC 945, a novel tumor-selective thymidylate synthase inhibitor targeted to alpha-folate receptor-overexpressing tumors. Cancer Res. 2005 Dec 15;65(24):11721-8.
[3]. Chau Ng, et al. Efficacy and tolerability of the thymidylate synthase (TS) inhibitor, BGC 945 is mediated through its selective uptake via the α-folate receptor (α-FR) in IGROV-1 human tumor xenografts. AACR Annual Meeting– Apr 12-16, 2008; San Diego, CA.
ONX 0801 (BGC 945) trisodium is a thymidylate synthase (TS) inhibitor, targeted to α-folate receptor–overexpressing tumors[1][2].
体外研究 (In Vitro)
ONX 0801 (BGC 945) is designed to further reduce toxicity by more effectively targeting cancer cells that overexpress the α-FR[1]. ONX 0801 (BGC 945) exhibits IC50 values of of 6.6 μM, 1.1 nM, 3.3 nM, 90 nM and 0.32 μM in A431, A431-FBP, KB, IGROV-1 and JEG-3 cells[2].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
体内研究 (In Vivo)
BGC 945 (100 mg/kg, ip/iv injection) in the tumor had a longer half-life (28 hours) compared with other tissues[2]. BGC 945 (100 mg/kg daily for 16 days) does not lead to body weight loss, macroscopic signs of toxicity to the major organs, or a change in renal function[2]. BGC 945 at 100mg/kg induces a 5-20-fold increase in tumor dUrd at 4-72h without increases in the plasma, consistent with tumor targeting[2].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
Animal Model:
Mice (on the folate-free diet for 5 days were transplanted with tumor and the implants)[2].
Dosage:
100 mg/kg (Pharmacokinetic Analysis).
Administration:
Single i.p. or iv injection.
Result:
After i.p. injection, the compound was well absorbed from the peritoneal cavity. The plasma AUC was 50% higher for i.p. compared with i.v. administration and was also higher in spleen, kidney, and liver by this route. Tumor AUC was similar via either route.
分子量
713.58
Formula
C32H30N5Na3O10
CAS 号
1097638-00-0
运输条件
Room temperature in continental US; may vary elsewhere.
储存方式
Please store the product under the recommended conditions in the Certificate of Analysis.
参考文献
[1]. Anna Tochowicz, et al. Development and binding mode assessment of N-[4-[2-propyn-1-yl[(6S)-4,6,7,8-tetrahydro-2-(hydroxymethyl)-4-oxo-3H-cyclopenta[g]quinazolin-6-yl]amino]benzoyl]-l-γ-glutamyl-D-glutamic acid (BGC 945), a novel thymidylate synthase inhibitor that targets tumor cells. J Med Chem. 2013 Jul 11;56(13):5446-55.
[2]. David D Gibbs, et al. BGC 945, a novel tumor-selective thymidylate synthase inhibitor targeted to alpha-folate receptor-overexpressing tumors. Cancer Res. 2005 Dec 15;65(24):11721-8.
[3]. Chau Ng, et al. Efficacy and tolerability of the thymidylate synthase (TS) inhibitor, BGC 945 is mediated through its selective uptake via the α-folate receptor (α-FR) in IGROV-1 human tumor xenografts. AACR Annual Meeting– Apr 12-16, 2008; San Diego, CA.
ONX 0801 (BGC 945) trisodium is a thymidylate synthase (TS) inhibitor, targeted to α-folate receptor–overexpressing tumors[1][2].
体外研究 (In Vitro)
ONX 0801 (BGC 945) is designed to further reduce toxicity by more effectively targeting cancer cells that overexpress the α-FR[1]. ONX 0801 (BGC 945) exhibits IC50 values of of 6.6 μM, 1.1 nM, 3.3 nM, 90 nM and 0.32 μM in A431, A431-FBP, KB, IGROV-1 and JEG-3 cells[2].
Shanghai Jinpan Biotech Co Ltd has not independently confirmed the accuracy of these methods. They are for reference only.
体内研究 (In Vivo)
BGC 945 (100 mg/kg, ip/iv injection) in the tumor had a longer half-life (28 hours) compared with other tissues[2]. BGC 945 (100 mg/kg daily for 16 days) does not lead to body weight loss, macroscopic signs of toxicity to the major organs, or a change in renal function[2]. BGC 945 at 100mg/kg induces a 5-20-fold increase in tumor dUrd at 4-72h without increases in the plasma, consistent with tumor targeting[2].
Shanghai Jinpan Biotech Co Ltd has not independently confirmed the accuracy of these methods. They are for reference only.
Animal Model:
Mice (on the folate-free diet for 5 days were transplanted with tumor and the implants)[2].
Dosage:
100 mg/kg (Pharmacokinetic Analysis).
Administration:
Single i.p. or iv injection.
Result:
After i.p. injection, the compound was well absorbed from the peritoneal cavity. The plasma AUC was 50% higher for i.p. compared with i.v. administration and was also higher in spleen, kidney, and liver by this route. Tumor AUC was similar via either route.
分子量
713.58
Formula
C32H30N5Na3O10
CAS 号
1097638-00-0
运输条件
Room temperature in continental US; may vary elsewhere.
储存方式
Please store the product under the recommended conditions in the Certificate of Analysis.
参考文献
[1]. Anna Tochowicz, et al. Development and binding mode assessment of N-[4-[2-propyn-1-yl[(6S)-4,6,7,8-tetrahydro-2-(hydroxymethyl)-4-oxo-3H-cyclopenta[g]quinazolin-6-yl]amino]benzoyl]-l-γ-glutamyl-D-glutamic acid (BGC 945), a novel thymidylate synthase inhibitor that targets tumor cells. J Med Chem. 2013 Jul 11;56(13):5446-55.
[2]. David D Gibbs, et al. BGC 945, a novel tumor-selective thymidylate synthase inhibitor targeted to alpha-folate receptor-overexpressing tumors. Cancer Res. 2005 Dec 15;65(24):11721-8.
[3]. Chau Ng, et al. Efficacy and tolerability of the thymidylate synthase (TS) inhibitor, BGC 945 is mediated through its selective uptake via the α-folate receptor (α-FR) in IGROV-1 human tumor xenografts. AACR Annual Meeting– Apr 12-16, 2008; San Diego, CA.
Oprozomib (PR-047) is an orally bioavailable and selective peptide epoxyketone proteasome inhibitor with IC50s of 36 and 82 nM for proteasome (β5) and immunoproteasome (LMP7), respectively. Oprozomib (ONX 0912) induces apoptosis in MM cells[1].
体外研究 (In Vitro)
Oprozomib inhibits 20S chymotrypsin-like (CT-L) with an IC50 of 55 ± 19 nM. Oprozomib inhibits human leukemia Molt-4 cells CT-L with an IC50 of 66 nM[1]. Oprozomib (ONX 0912; 1-1000 nM; 48 hours) significantly decreases the viability of human multiple myeloma (MM) cell lines[2]. The anti-MM activity of Oprozomib is associated with activation of caspase-8, caspase-9, caspase-3, and PARP[2].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
Cell Viability Assay[2]
Cell Line:
Human MM cell lines (MM.1S, INA-6, RPMI-8226, MM.1R, Dox-40, KMS12, and OPM2)
Concentration:
1, 10, 100, 1000 nM
Incubation Time:
48 hours
Result:
Exhibited anti-MM activity.
Western Blot Analysis[2]
Cell Line:
MM.1S cells
Concentration:
7 nM and 10 nM
Incubation Time:
48 hours
Result:
Treatment with 3nM triggered a marked increase in proteolytic cleavage of PARP, a signature event during apoptosis. Induced cleavage of caspase-3, an upstream activator of PARP. Induced activation of both casapse-8 (extrinsic) and caspase-9 (intrinsic) apoptotic pathways.
体内研究 (In Vivo)
Oprozomib (PR-047) selectively inhibits chymotrypsin-like (CT-L) activity of both the constitutive proteasome (β5) and immunoproteasome (LMP7) and demonstrates an absolute bioavailability of up to 39% in rodents and dogs[1]. Oprozomib promotes antitumor activity in multiple animal models by oral administration at doses below the maximum tolerated dose (MTD)[1]. Oprozomib (30 mg/kg by oral gavage once daily for 5 consecutive days followed by 2 days of rest) treatment decreases tumor burden in C57Bl/6 and NOD.SCID.IL2Rγ-/- mice[3].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
Animal Model:
C57Bl/6 and NOD.SCID.IL2Rγ-/- mice bearing established human RPMI-8226-luc myeloma cells[3]
Dosage:
30 mg/kg
Administration:
Oral gavage once daily for 5 consecutive days followed by 2 days of rest
Result:
Decreased human MM tumor burden and protects mice from bone destruction.
Clinical Trial
分子量
532.61
Formula
C25H32N4O7S
CAS 号
935888-69-0
中文名称
奥泼佐米
运输条件
Room temperature in continental US; may vary elsewhere.
[1]. Han-Jie Zhou, et al. Design and synthesis of an orally bioavailable and selective peptide epoxyketone proteasome inhibitor (PR-047). J Med Chem. 2009 May 14;52(9):3028-38.
[2]. Dharminder Chauhan,et al. A novel orally active proteasome inhibitor ONX 0912 triggers in vitro and in vivo cytotoxicity in multiple myeloma. Blood. 2010 Dec 2;116(23):4906-15.
[3]. M A Hurchla, et al.The epoxyketone-based proteasome inhibitors carfilzomib and orally bioavailable oprozomib have anti-resorptive and bone-anabolic activity in addition to anti-myeloma effects. Leukemia. 2013 Feb;27(2):430-40.
