MedKoo Cat#: 100544 | Name: Lobaplatin
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Description:

WARNING: This product is for research use only, not for human or veterinary use.

Lobaplatin (D-19466) is a diastereometric mixture of platinum(II) complexes containing a 1,2-bis(aminomethyl)cyclobutane stable ligand and lactic acid as the leaving group. Its antitumour activity results from the formation of DNA-drug adducts, mainly as GG and AG intra-strand cross-links. Lobaplatin influences the expression of the c-myc gene, which is involved in oncogenesis, apoptosis and cell proliferation. Lobaplatin has activity in a wide range of preclinical tumour models and appears to overcome tumour resistance to cisplatin and carboplatin in some of these models. In the body, lobaplatin remains largely intact until removed by glomerular filtration. (source: Expert Opin Investig Drugs. 2001 Jan;10(1):119-28.).

Chemical Structure

Lobaplatin
Lobaplatin
CAS#135558-11-1

Theoretical Analysis

MedKoo Cat#: 100544

Name: Lobaplatin

CAS#: 135558-11-1

Chemical Formula: C9H18N2O3Pt

Exact Mass: 0.0000

Molecular Weight: 397.34

Elemental Analysis: C, 27.21; H, 4.57; N, 7.05; O, 12.08; Pt, 49.10

Price and Availability

Size Price Availability Quantity
100mg USD 1,650.00 2 Weeks
200mg USD 2,950.00 2 Weeks
500mg USD 3,950.00 2 Weeks
1g USD 6,450.00 2 Weeks
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Related CAS #
No Data
Synonym
D19466; D-19466; Lobaplatin.
IUPAC/Chemical Name
cis-[(1R*,2R*)-1,2-Cyclobutanebis(methylamino)-N,N'][(2S)-2-hydroxypropanoato(2-)-O1,O2]platinum
InChi Key
RLXPIABKJFUYFG-UHFFFAOYSA-M
InChi Code
InChI=1S/C6H14N2.C3H5O3.Pt/c7-3-5-1-2-6(5)4-8;1-2(4)3(5)6;/h5-6H,1-4,7-8H2;2H,1H3,(H,5,6);/q;-1;+2/p-1
SMILES Code
CC([O-]1)C([O-][Pt]21[NH2+]CC(CC3)C3C[NH2+]2)=O.
Appearance
Solid powder
Purity
>98% (or refer to the Certificate of Analysis)
Shipping Condition
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility
Soluble in DMSO, not in water
Shelf Life
>2 years if stored properly
Drug Formulation
This drug may be formulated in DMSO
Stock Solution Storage
0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code
2934.99.9001
More Info
Lobaplatin [D 19466] is a platinum complex with DNA alkylating activity that was developed by ASTA Medica (Degussa) for the treatment of cancer. ASTA Medica discontinued development of lobaplatin, and subsequent development of the compound became the responsibility of Zentaris AG (AEterna Laboratories), which was formed in 2001 from the biopharmaceutical, inhalation technology and gene therapy activities of ASTA Medica. On 30 December 2002, Zentaris was acquired by AEterna Laboratories. Cisplatin, one of the original platinum compounds, has had a major impact on the treatment of solid tumours such as germ cell cancer, ovarian cancer, bladder cancer and bronchial carcinoma, but its clinical usefulness is limited by renal, neurological and gastrointestinal toxicity. This has led to the development of second- and third-generation platinum analogues, such as lobaplatin, with reduced toxicity and a better therapeutic index. In January 2003, Zentaris AG and Hainan Tianwang International Pharmaceutical signed a contract for the manufacture and marketing of lobaplatin in China. The technology transfer agreement provides for Zentaris to receive a one-time payment to the amount of 4.5 million Canadian dollars. In addition, the contract foresees for Tianwang to manufacture and deliver lobaplatin to Zentaris or its partners for marketing in all other countries worldwide. Lobaplatin has been approved in China for the treatment of chronic myelogenous leukaemia (CML) and inoperable, metastatic breast and small cell lung cancer. However, it has not yet been launched there. In June 2003, AEterna reported that it expects lobaplatin to be launched in China by the end of 2003 at the 10th Annual Meeting of the Biotechnology Industry Organization (BIO-2003). Lobaplatin has also completed phase II clinical trials in the US, Australia, EU, Brazil and South Africa for the treatment of various cancers, including breast, oesophageal, lung and ovarian cancers as well as CML . see: Drugs R D. 2003;4(6):369-72. http://www.ncbi.nlm.nih.gov/pubmed/14584968 . Phase I clinical trials of three quite different administration schedules found the same dose-limiting toxicity (thrombocytopoenia) and similar maximum tolerated doses (60 mg/m(2) per 3 - 4 weeks). In Phase II trials, lobaplatin showed activity in patients with a variety of tumour types. Many of the patients who responded to lobaplatin may also have responded to cisplatin and carboplatin because they had had no prior chemotherapy or had a prolonged remission after earlier treatment. In conclusion, lobaplatin is a new platinum drug, which overcomes some forms of cisplatin resistance in preclinical tumour models. Several potential clinical applications remain unexplored, such as its use in relapsed testicular cancer and in combination with other cancer chemotherapeutic agents and ionising radiation.        
Product Data
Biological target:
Lobaplatin induces apoptosis by increasing expressions of caspase and Bax, decreasing expression of Bcl-2.
In vitro activity:
Lobaplatin inhibited proliferation of human HCC cells in a dose-dependent manner. For the most sensitive SMMC-7721 cells, lobaplatin arrested cell cycle progression in G1 and G2/M phases time-dependently which might be associated with the down-regulation of cyclin B, CDK1, CDC25C, phosphorylated CDK1 (pCDK1), pCDK4, Rb, E2F, and pRb, and the up-regulation of p53, p21, and p27. Reference: J Hematol Oncol. 2010 Oct 31;3:43. https://pubmed.ncbi.nlm.nih.gov/21034513/
In vivo activity:
In vivo study showed that Lobaplatin suppressed tumor growth of EC-109 xenograft. Lobaplatin significantly inhibited the growth of esophageal squamous cell carcinoma by inducing apoptosis through the caspase-dependent pathway. Reference: Biomed Pharmacother. 2017 Nov;95:447-452. https://pubmed.ncbi.nlm.nih.gov/28865364/
Solvent mg/mL mM
Solubility
Ethanol 4.0 10.07
Water 28.5 71.73
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 397.34 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Recalculate based on batch purity %
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.15 mL 5.76 mL 11.51 mL
5 mM 0.23 mL 1.15 mL 2.3 mL
10 mM 0.12 mL 0.58 mL 1.15 mL
50 mM 0.02 mL 0.12 mL 0.23 mL
Formulation protocol:
1. Li D, Wang WJ, Wang YZ, Wang YB, Li YL. Lobaplatin promotes 125I-induced apoptosis and inhibition of proliferation in hepatocellular carcinoma by upregulating PERK-eIF2α-ATF4-CHOP pathway. Cell Death Dis. 2019 Oct 3;10(10):744. doi: 10.1038/s41419-019-1918-1. PMID: 31582720; PMCID: PMC6776519. 2. Wu Q, Qin SK, Teng FM, Chen CJ, Wang R. Lobaplatin arrests cell cycle progression in human hepatocellular carcinoma cells. J Hematol Oncol. 2010 Oct 31;3:43. doi: 10.1186/1756-8722-3-43. PMID: 21034513; PMCID: PMC2988698. 3. Du L, Fei Z, Song S, Wei N. Antitumor activity of Lobaplatin against esophageal squamous cell carcinoma through caspase-dependent apoptosis and increasing the Bax/Bcl-2 ratio. Biomed Pharmacother. 2017 Nov;95:447-452. doi: 10.1016/j.biopha.2017.08.119. Epub 2017 Sep 12. PMID: 28865364. 4. Voegeli R, Schumacher W, Engel J, Respondek J, Hilgard P. D-19466, a new cyclobutane-platinum complex with antitumor activity. J Cancer Res Clin Oncol. 1990;116(5):439-42. doi: 10.1007/BF01612990. PMID: 2229133.
In vitro protocol:
1. Li D, Wang WJ, Wang YZ, Wang YB, Li YL. Lobaplatin promotes 125I-induced apoptosis and inhibition of proliferation in hepatocellular carcinoma by upregulating PERK-eIF2α-ATF4-CHOP pathway. Cell Death Dis. 2019 Oct 3;10(10):744. doi: 10.1038/s41419-019-1918-1. PMID: 31582720; PMCID: PMC6776519. 2. Wu Q, Qin SK, Teng FM, Chen CJ, Wang R. Lobaplatin arrests cell cycle progression in human hepatocellular carcinoma cells. J Hematol Oncol. 2010 Oct 31;3:43. doi: 10.1186/1756-8722-3-43. PMID: 21034513; PMCID: PMC2988698.
In vivo protocol:
1. Du L, Fei Z, Song S, Wei N. Antitumor activity of Lobaplatin against esophageal squamous cell carcinoma through caspase-dependent apoptosis and increasing the Bax/Bcl-2 ratio. Biomed Pharmacother. 2017 Nov;95:447-452. doi: 10.1016/j.biopha.2017.08.119. Epub 2017 Sep 12. PMID: 28865364. 2. Voegeli R, Schumacher W, Engel J, Respondek J, Hilgard P. D-19466, a new cyclobutane-platinum complex with antitumor activity. J Cancer Res Clin Oncol. 1990;116(5):439-42. doi: 10.1007/BF01612990. PMID: 2229133.
1: Huang XE, Wei GL, Huo JG, Wang XN, Lu YY, Wu XY, Liu J, Xiang J, Feng JF. Intrapleural or intraperitoneal lobaplatin for treatment of patients with malignant pleural effusion or ascites. Asian Pac J Cancer Prev. 2013;14(4):2611-4. PubMed PMID: 23725184. 2: Deng QQ, Huang XE, Ye LH, Lu YY, Liang Y, Xiang J. Phase II trial of Loubo® (Lobaplatin) and pemetrexed for patients with metastatic breast cancer not responding to anthracycline or taxanes. Asian Pac J Cancer Prev. 2013;14(1):413-7. PubMed PMID: 23534764. 3: Wang Y, Zheng WL, Ma WL. Lobaplatin inhibits the proliferation of hepatollular carcinoma through p53 apoptosis axis. Hepat Mon. 2012 Oct;12(10 HCC):e6024. doi: 10.5812/hepatmon.6024. Epub 2012 Oct 11. PubMed PMID: 23193415; PubMed Central PMCID: PMC3500997. 4: Xie CY, Xu YP, Jin W, Lou LG. Antitumor activity of lobaplatin alone or in combination with antitubulin agents in non-small-cell lung cancer. Anticancer Drugs. 2012 Aug;23(7):698-705. doi: 10.1097/CAD.0b013e328352cc10. PubMed PMID: 22441567. 5: Wang Z, Tang X, Zhang Y, Qi R, Li Z, Zhang K, Liu Z, Yang X. Lobaplatin induces apoptosis and arrests cell cycle progression in human cholangiocarcinoma cell line RBE. Biomed Pharmacother. 2012 Apr;66(3):161-6. doi: 10.1016/j.biopha.2011.09.008. Epub 2011 Dec 29. PubMed PMID: 22425181. 6: Engel JB, Martens T, Hahne JC, Häusler SF, Krockenberger M, Segerer S, Djakovic A, Meyer S, Dietl J, Wischhusen J, Honig A. Effects of lobaplatin as a single agent and in combination with TRAIL on the growth of triple-negative p53-mutated breast cancers in vitro. Anticancer Drugs. 2012 Apr;23(4):426-36. doi: 10.1097/CAD.0b013e32834fb8ce. PubMed PMID: 22314264. 7: Dai HY, Liu L, Qin SK, He XM, Li SY. Lobaplatin suppresses proliferation and induces apoptosis in the human colorectal carcinoma cell Line LOVO in vitro. Biomed Pharmacother. 2011 Jun;65(3):137-41. doi: 10.1016/j.biopha.2010.12.001. Epub 2010 Dec 30. PubMed PMID: 21612887. 8: Wu Q, Qin SK, Teng FM, Chen CJ, Wang R. Lobaplatin arrests cell cycle progression in human hepatocellular carcinoma cells. J Hematol Oncol. 2010 Oct 31;3:43. doi: 10.1186/1756-8722-3-43. PubMed PMID: 21034513; PubMed Central PMCID: PMC2988698. 9: Zhou B, Shan H, Zhu KS, Jiang ZB, Guan SH, Meng XC, Zeng XC. Chemoembolization with lobaplatin mixed with iodized oil for unresectable recurrent hepatocellular carcinoma after orthotopic liver transplantation. J Vasc Interv Radiol. 2010 Mar;21(3):333-8. doi: 10.1016/j.jvir.2009.11.006. Epub 2010 Feb 8. PubMed PMID: 20116286. (Last updated: 4/18/2016).