LB-100 | CAS#1632032-53-1 | 2A(PP2A)inhibitor

MedKoo Cat#: 206834 | Name: LB-100

Description:

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

LB-100 is a protein phosphatase 2A(PP2A)inhibitor. LB-100 sensitizes hepatocellular carcinoma cells to the effects of sorafenib during hypoxia by activation of Smad3 phosphorylation. LB-100 enhanced the effects of sorafenib in HCC cells only during hypoxic environments. LB-100 dramatically increased intracellular p-Smad3 level, which was responsible for the effect of LB-100 as a sensitizer. LB-100 downregulated Bcl-2 expression and enhanced sorafenib-induced apoptosis in HCC cells.

Chemical Structure

LB-100

CAS#1632032-53-1

Theoretical Analysis

MedKoo Cat#: 206834

Name: LB-100

CAS#: 1632032-53-1

Chemical Formula: C13H20N2O4

Exact Mass: 268.1423

Molecular Weight: 268.31

Elemental Analysis: C, 58.19; H, 7.51; N, 10.44; O, 23.85

Price and Availability

Size	Price	Availability
10mg	USD 150.00	Ready to ship
25mg	USD 250.00	Ready to ship
50mg	USD 450.00	Ready to ship
100mg	USD 750.00	Ready to ship
200mg	USD 1,350.00	Ready to ship
500mg	USD 2,850.00	Ready to ship

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Related CAS #

1632032-53-1 1026680-07-8 (deleted)

Synonym

LB-100; LB 100; LB100.

IUPAC/Chemical Name

3-[(4-Methylpiperazin-1-yl)carbonyl]-7-oxabicyclo[2.2.1]heptane-2-carboxylic acid

InChi Key

JUQMLSGOTNKJKI-UHFFFAOYSA-N

InChi Code

InChI=1S/C13H20N2O4/c1-14-4-6-15(7-5-14)12(16)10-8-2-3-9(19-8)11(10)13(17)18/h8-11H,2-7H2,1H3,(H,17,18)

SMILES Code

O=C(C1C(O2)CCC2C1C(N3CCN(C)CC3)=O)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 and 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

Product Data

Product Data

Certificate of Analysis

View CoA: current batch, Lot#A7T11K17

View CoA: current batch, Lot#A22T07K15

QC Data

View QC data: current batch, Lot#A22T07K15

View QC data: current batch, Lot#A7T11K17

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

Biological target:

LB-100 is a water soluble protein phosphatase 2A (PP2A) inhibitor with IC50s of 0.85 μM and 3.87 μM in BxPc-3 and Panc-1 cells.

In vitro activity:

A panel of TNBC cell lines were treated with LB-100 and growth inhibition was determined by MTT assay. Figure 1(a) shows that LB-100 effectively inhibited the growth of all cell lines tested with IC50 ranging from 1.17 to 7.145 μM. To confirm if such inhibitory effect applies to TNBC cells that have acquired TRAIL resistance, we tested the effects of LB-100 on growth inhibition using two TRAIL-resistant TNBC cell models. To establish TRAIL-resistant SUM159 (SUM159-R) and MDA213 (MDA231-R) cells, TRAIL-sensitive SUM159 and MDA231 (SUM159-P and MDA231-P, respectively) were exposed to gradually increased concentrations of TRAIL starting from 5 ng to 120 ng/ml for over a 6-month duration. We treated SUM159-P/SUM159-R and MDA231-P/MDA231-R cells with various doses of LB-100 for 72 h, and MTT was performed and IC50 value was calculated. While the IC50 for TRAIL in SUM159-P and SUM159-R cells were 10.7 ng/ml and >1000 ng/ml, respectively, both cell lines were equally sensitive to LB-100, reflected by IC50 value of LB-100 being 3.83 μM and 3.81 μM, respectively (Figure 2). Similar results were obtained with MDA231-P/MDA231-R cells. These data suggest that LB-100 effectively inhibits the growth of TNBC cells regardless of the status of TRAIL sensitivity. Reference: Cell Cycle. 2020 Mar;19(5):592-600. https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/32011210/

In vivo activity:

ELISA assays showed that pancreatic cancer cells secreted 1.5 to 2 times more VEGF when exposed to LB-100 (Fig. 3A). The microvessel density was checked in all xenografts mentioned above. Using immunohistochemical measurement of CD31, we found a significantly higher density of microvessel in tumors of mice with treated LB-100 (Fig. 3B and C). In addition, LB-100 injection resulted in rapid blood flow at the surface of tumors in mice (Fig. 3D), assessed by Doppler measurement. More doxorubicin accumulated within tumors in mice treated with LB-100 as judged by stronger intensity of doxorubicin specific fluorescence (Fig. 3E). Taken together these results suggest that PP2A inhibition by LB-100 led to higher perfusion and consequently more doxorubicin within tumors. Reference: Cancer Lett. 2014 Dec 28;355(2):281-7. https://linkinghub.elsevier.com/retrieve/pii/S0304-3835(14)00589-8

	Solvent	mg/mL	mM
Solubility
	DMSO	54.0	201.26

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 268.31 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.

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:

In vitro protocol:

1. Bai X, Zhi X, Zhang Q, Liang F, Chen W, Liang C, Hu Q, Sun X, Zhuang Z, Liang T. Inhibition of protein phosphatase 2A sensitizes pancreatic cancer to chemotherapy by increasing drug perfusion via HIF-1α-VEGF mediated angiogenesis. Cancer Lett. 2014 Dec 28;355(2):281-7. doi: 10.1016/j.canlet.2014.09.048. Epub 2014 Oct 7. PMID: 25304380. 2. Uddin MH, Pimentel JM, Chatterjee M, Allen JE, Zhuang Z, Wu GS. Targeting PP2A inhibits the growth of triple-negative breast cancer cells. Cell Cycle. 2020 Mar;19(5):592-600. doi: 10.1080/15384101.2020.1723195. Epub 2020 Feb 3. PMID: 32011210; PMCID: PMC7100985.

In vivo protocol:

1. Bai X, Zhi X, Zhang Q, Liang F, Chen W, Liang C, Hu Q, Sun X, Zhuang Z, Liang T. Inhibition of protein phosphatase 2A sensitizes pancreatic cancer to chemotherapy by increasing drug perfusion via HIF-1α-VEGF mediated angiogenesis. Cancer Lett. 2014 Dec 28;355(2):281-7. doi: 10.1016/j.canlet.2014.09.048. Epub 2014 Oct 7. PMID: 25304380. 2. Maggio D, Ho WS, Breese R, Walbridge S, Wang H, Cui J, Heiss JD, Gilbert MR, Kovach JS, Lu RO, Zhuang Z. Inhibition of protein phosphatase-2A with LB-100 enhances antitumor immunity against glioblastoma. J Neurooncol. 2020 Jun;148(2):231-244. doi: 10.1007/s11060-020-03517-5. Epub 2020 Apr 27. PMID: 32342332; PMCID: PMC7467059.

1: Fu QH, Zhang Q, Zhang JY, Sun X, Lou Y, Li GG, Chen ZL, Bai XL, Liang TB. LB-100 sensitizes hepatocellular carcinoma cells to the effects of sorafenib during hypoxia by activation of Smad3 phosphorylation. Tumour Biol. 2016 Jun;37(6):7277-86. doi: 10.1007/s13277-015-4560-2. Epub 2015 Dec 14. PubMed PMID: 26666823. 2: Chung V, Mansfield AS, Braiteh F, Richards D, Durivage H, Ungerleider RS, Johnson F, Kovach JS. Safety, Tolerability, and Preliminary Activity of LB-100, an Inhibitor of Protein Phosphatase 2A, in Patients with Relapsed Solid Tumors: An Open-Label, Dose Escalation, First-in-Human, Phase I Trial. Clin Cancer Res. 2016 Dec 30. doi: 10.1158/1078-0432.CCR-16-2299. [Epub ahead of print] PubMed PMID: 28039265. 3: Bai XL, Zhang Q, Ye LY, Hu QD, Fu QH, Zhi X, Su W, Su RG, Ma T, Chen W, Xie SZ, Chen CL, Liang TB. Inhibition of protein phosphatase 2A enhances cytotoxicity and accessibility of chemotherapeutic drugs to hepatocellular carcinomas. Mol Cancer Ther. 2014 Aug;13(8):2062-72. doi: 10.1158/1535-7163.MCT-13-0800. Epub 2014 May 27. PubMed PMID: 24867249. 4: Bai X, Zhi X, Zhang Q, Liang F, Chen W, Liang C, Hu Q, Sun X, Zhuang Z, Liang T. Inhibition of protein phosphatase 2A sensitizes pancreatic cancer to chemotherapy by increasing drug perfusion via HIF-1α-VEGF mediated angiogenesis. Cancer Lett. 2014 Dec 28;355(2):281-7. doi: 10.1016/j.canlet.2014.09.048. Epub 2014 Oct 7. PubMed PMID: 25304380. 5: Nyholm D, Lewander T, Gomes-Trolin C, Bäckström T, Panagiotidis G, Ehrnebo M, Nyström C, Aquilonius SM. Pharmacokinetics of levodopa/carbidopa microtablets versus levodopa/benserazide and levodopa/carbidopa in healthy volunteers. Clin Neuropharmacol. 2012 May-Jun;35(3):111-7. doi: 10.1097/WNF.0b013e31825645d1. PubMed PMID: 22549097. 6: Lecca S, Pelosi A, Tchenio A, Moutkine I, Lujan R, Hervé D, Mameli M. Rescue of GABAB and GIRK function in the lateral habenula by protein phosphatase 2A inhibition ameliorates depression-like phenotypes in mice. Nat Med. 2016 Mar;22(3):254-61. doi: 10.1038/nm.4037. Epub 2016 Jan 25. PubMed PMID: 26808347. 7: Zhang C, Hong CS, Hu X, Yang C, Wang H, Zhu D, Moon S, Dmitriev P, Lu J, Chiang J, Zhuang Z, Zhou Y. Inhibition of protein phosphatase 2A with the small molecule LB100 overcomes cell cycle arrest in osteosarcoma after cisplatin treatment. Cell Cycle. 2015;14(13):2100-8. doi: 10.1080/15384101.2015.1041693. Epub 2015 May 5. PubMed PMID: 25942376; PubMed Central PMCID: PMC4612123. 8: Gordon IK, Lu J, Graves CA, Huntoon K, Frerich JM, Hanson RH, Wang X, Hong CS, Ho W, Feldman MJ, Ikejiri B, Bisht K, Chen XS, Tandle A, Yang C, Arscott WT, Ye D, Heiss JD, Lonser RR, Camphausen K, Zhuang Z. Protein Phosphatase 2A Inhibition with LB100 Enhances Radiation-Induced Mitotic Catastrophe and Tumor Growth Delay in Glioblastoma. Mol Cancer Ther. 2015 Jul;14(7):1540-7. doi: 10.1158/1535-7163.MCT-14-0614. Epub 2015 May 4. PubMed PMID: 25939762; PubMed Central PMCID: PMC4497833. 9: Hong CS, Ho W, Zhang C, Yang C, Elder JB, Zhuang Z. LB100, a small molecule inhibitor of PP2A with potent chemo- and radio-sensitizing potential. Cancer Biol Ther. 2015;16(6):821-33. doi: 10.1080/15384047.2015.1040961. Epub 2015 Apr 21. Review. PubMed PMID: 25897893; PubMed Central PMCID: PMC4623051. 10: Chang KE, Wei BR, Madigan JP, Hall MD, Simpson RM, Zhuang Z, Gottesman MM. The protein phosphatase 2A inhibitor LB100 sensitizes ovarian carcinoma cells to cisplatin-mediated cytotoxicity. Mol Cancer Ther. 2015 Jan;14(1):90-100. doi: 10.1158/1535-7163.MCT-14-0496. Epub 2014 Nov 5. PubMed PMID: 25376608; PubMed Central PMCID: PMC4557740. 11: Lembo M, Cannatà V, Militello A, Ritrovato M, Zaffina S, Derrico P, Borra M. [Artificial lighting and blue light in the operating room: what risks for the surgeon?]. Med Lav. 2015 Sep 9;106(5):342-50. Italian. PubMed PMID: 26384260. 12: Vaillant A, Dentan G, Laurent Y, Aurélie G, Beer JC, Germin F, Boch É, Casillas JM, Brunel P, Touzery C, Cottin Y, Zeller M, Morel G; pour le réseau de prise en charge et de prévention des infarctus du myocarde de Côte-d’Or (RPC-PIM).. The Log book for the secondary prevention of coronary artery disease: A pilot study. Presse Med. 2015 Sep;44(9):e301-9. doi: 10.1016/j.lpm.2014.11.020. Epub 2015 Jul 2. PubMed PMID: 26144276. 13: Broadhurst T, Huang X, Frye B, Ellis R. A Spectroscopic Redshift for the Cl 0024+16 Multiple Arc System: Implications for the Central Mass Distribution. Astrophys J. 2000 May 1;534(1):L15-L18. PubMed PMID: 10790060. 14: Taylor EN, Stampfer MJ, Curhan GC. Obesity, weight gain, and the risk of kidney stones. JAMA. 2005 Jan 26;293(4):455-62. PubMed PMID: 15671430.