A8648-200mg | Oxaliplatin [61825-94-3] Clinisciences

Oxaliplatin inhibits DNA synthesis, primarily by conforming DNA adducts. Oxaliplatin, a platinum compound, has a broad spectrum of anti-tumor activity and has demonstrated a lack of cross-resistance with other platinum compounds. Oxaliplatin induces primary and secondary DNA lesions that lead to cell apoptosis.

In vitro: Oxaliplatin is active against human melanoma cell lines C32 and G361 with the IC50 values of 0.98 mM and 0.14 mM, respectively. Oxaliplatin effectively inhibited bladder carcinoma cell lines RT4 and TCCSUP, ovarian carcinoma cell line A2780, colon carcinoma cell line HT-29, glioblastoma cell lines U-87MG and U-373MG, and melanoma cell lines SK-MEL-2 and HT-144 with the IC50 values of 11 μM, 15 μM, 0.17 μM, 0.97 μM, 17.6 μM, 2.95 μM, 30.9 μM and 7.85 μM, respectively.

In vivo: A weekly injection of Oxaliplatin (10 mg/kg, i.p.) to nude mice bearing hepatocellular HCCLM3 tumors significantly reduces tumor volume and apoptotic index. Oxaliplatin (5 mg/kg, i.v. on days 1, 5 and 9) was active on T-leukemia-lymphoma L40 AKR with T/C of 1.77. Oxaliplatin was also efficient on intracerebrally grafted L1210 leukemia, B16 melanoma xenografts, MA 16-C xenografts, Lewis lung xenografts and C26 colon carcinoma xenografts. Oxaliplatin induced impairment of retrograde neuronal transport in mice.

Clinical Trials: In patients with metastatic colorectal cancer, in combination with fluorouracil/folinic acid, Oxaliplatin showed its activity against metastatic colorectal, both as a first-line therapy and in patients refractory to previous chemotherapy. In addition, oxaliplatin has also shown efficacy in patients with platinum-pretreated ovarian cancer, non-Hodgkin's lymphoma, breast cancer, mesothelioma and non-small cell lung cancer.

References:
[1]. Culy CR, Clemett D, Wiseman LR. Oxaliplatin.A review of its pharmacological properties and clinical efficacy in metastatic colorectal cancer and its potential in other malignancies.Drugs. 2000 Oct;60(4):895-924.
[2]. Raymond E, Faivre S, Chaney S et al. Cellular and molecular pharmacology of oxaliplatin. Mol Cancer Ther. 2002 Jan;1(3):227-35.
[3]. Stein A, Arnold D. Oxaliplatin: a review of approved uses. Expert Opin Pharmacother. 2012 Jan;13(1):125-37.
[4]. Hoff PM, Saad ED, Costa F et al. Literature review and practical aspects on the management of oxaliplatin-associated toxicity. Clin Colorectal Cancer. 2012 Jun;11(2):93-100.
[5]. Hall MD, et al. Say no to DMSO: dimethylsulfoxide inactivates cisplatin, carboplatin, and other platinum complexes. Cancer Res. 2014 Jul 15;74(14):3913-22.

1. Qing Zhang, Yue Zhou, et al. "Low-dose orlistat promotes the therapeutic effect of oxaliplatin in colorectal cancer." Biomed Pharmacother. 2022 Sep;153:113426. PMID: 36017794
2. Xia Liao, Yaoyao Zhang, et al. "Inositol hexaphosphate sensitizes hepatocellular carcinoma to oxaliplatin relating inhibition of CCN2-LRP6-β-catenin-ABCG1 signaling pathway." J Cancer. 2021 Aug 24;12(20):6071-6080. PMID: 34539880
3. Liao X, Song G, et al. "Oxaliplatin resistance is enhanced by saracatinib via upregulation Wnt-ABCG1 signaling in hepatocellular carcinoma." BMC Cancer. 2020;20(1):31. PMID: 31931755
4. Feng M, Jin JQ, et al. "Pharmacological inhibition of β-catenin/BCL9 interaction overcomes resistance to immune checkpoint blockades by modulating T(reg) cells." Sci Adv. 2019 May 8;5(5):eaau5240. PMID: 31086813
5. Cho SY, Chae J, et al. "Unstable Genome and Transcriptome Dynamics during Tumor Metastasis Contribute to Therapeutic Heterogeneity in Colorectal Cancers." Clin Cancer Res. 2019 Jan 22. PMID: 30670495
6. Goodspeed A, Jean A, et al. "A Whole-genome CRISPR Screen Identifies a Role of MSH2 in Cisplatin-mediated Cell Death in Muscle-invasive Bladder Cancer." Eur Urol. 2019 Feb;75(2):242-250. PMID: 30414698
7. Andrew Goodspeed, Annie Jean, et al. "Low MSH2 protein levels identify muscle-invasive bladder cancer resistant to cisplatin." bioRxiv. 2018 June 29.

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Physical Appearance	A solid
Storage	Store at -20°C
M.Wt	397.29
Cas No.	61825-94-3
Formula	C₈H₁₄N₂O₄Pt
Solubility	insoluble in EtOH; ≥37.25 mg/mL in DMSO; ≥3.94 mg/mL in H2O with gentle warming
Chemical Name	(1R,2R)-cyclohexane-1,2-diamine;oxalate;platinum(2+)
SDF	Download SDF
Canonical SMILES	C1CCC(C(C1)N)N.C(=O)(C(=O)[O-])[O-].[Pt+2]
Shipping Condition	Small Molecules with Blue Ice, Modified Nucleotides with Dry Ice.
General tips	We do not recommend long-term storage for the solution, please use it up soon.

Cell experiment [1,2]:
Cell lines	Carcinoma cell lines
Preparation method	Limited soluble in DMSO. General tips for obtaining a higher concentration: Please warm the tube at 37 ℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months.
Reacting condition	1-24h
Applications	Oxaliplatin effectively inhibited bladder carcinoma cell lines RT4 and TCCSUP, ovarian carcinoma cell line A2780, colon carcinoma cell line HT-29, glioblastoma cell lines U-373MG and U-87MG, and melanoma cell lines SK-MEL-2 and HT-144 with IC50 of 11 μM, 15 μM, 0.17 μM, 0.97 μM, 2.95 μM, 17.6 μM, 30.9 μM and 7.85 μM, respectively.Oxaliplatin was active against C32 and G361 cell lines with IC50 values of 49.48 and 9.07 μM (1 h), 9.47 and 1.30 μM (4 h), and 0.98 and 0.14 μM (24 h).
Animal experiment [3,4]:
Animal models	Nude mice bearing hepatocellular HCCLM3 tumors, Mice bearing L1210 leukemia, MA 16-C xenografts, B16 melanoma xenografts, Lewis lung xenografts and C26 colon carcinoma xenografts.
Dosage form	Intraperitoneal injection, 10 mg/kg, weekly injection; 5 mg/kg, Intravenous injection, on days 1, 5 and 9
Application	Oxaliplatin significantly reduced tumor volume and apoptotic index in nude mice bearing hepatocellular HCCLM3 tumors. Oxaliplatin (5 mg/kg, i.v. on days 1, 5 and 9) was active on T-leukemia-lymphoma L40 AKR with T/C of 1.77. Oxaliplatin was also efficient on intracerebrally grafted L1210 leukemia, B16 melanoma xenografts, MA 16-C xenografts, Lewis lung xenografts and C26 colon carcinoma xenografts. Oxaliplatin induced impairment of retrograde neuronal transport in mice.
Other notes	Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal.
References: [1]. Mohammed M Q, Retsas S. Oxaliplatin is active in vitro against human melanoma cell lines: comparison with cisplatin and carboplatin[J]. Anti-cancer drugs, 2000, 11(10): 859-863. [2]. Pendyala L, Creaven P J. In vitro cytotoxicity, protein binding, red blood cell partitioning, and biotransformation of oxaliplatin[J]. Cancer research, 1993, 53(24): 5970-5976. [3]. Wang Z, Zhou J, Fan J, et al. Oxaliplatin induces apoptosis in hepatocellular carcinoma cells and inhibits tumor growth[J]. Expert opinion on investigational drugs, 2009, 18(11): 1595-1604. [4]. Mathe G, Kidani Y, Segiguchi M, et al. Oxalato-platinum or 1-OHP, a third-generation platinum complex: an experimental and clinical appraisal and preliminary comparison with cis-platinum and carboplatinum[J]. Biomedicine & pharmacotherapy, 1989, 43(4): 237-250.