Synonym
BIBB 515; BIBB-515; BIBB515
IUPAC/Chemical Name
1-(4-Chlorobenzoyl)-4-((4-(2-oxazolin-2-yl) benzylidene))piperidine
InChi Key
JQNWPWUJMRAASQ-UHFFFAOYSA-N
InChi Code
InChI=1S/C22H21ClN2O2/c23-20-7-5-19(6-8-20)22(26)25-12-9-17(10-13-25)15-16-1-3-18(4-2-16)21-24-11-14-27-21/h1-8,15H,9-14H2
SMILES Code
O=C(N1CC/C(CC1)=C\C2=CC=C(C3=NCCO3)C=C2)C4=CC=C(Cl)C=C4
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
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
Biological target:
BIBB 515 is a 2,3-oxidosqualene cyclase (OSC) inhibitor.
In vitro activity:
Treatment of MEC-2 cells with BIBB-515 for 3 days resulted in about 20% decrease in total cellular cholesterol (Figure 4A). As shown in Figure 4D, E, F and G, BIBB-515 slightly intensified CD-20 immunostaining, and dramatically increased CD-20 membrane association which would, in turn, lead to increased signaling through CD-20 to downstream pathways. BIBB-515 also enhanced chemoimmuno-sensitivity in the cells treated with fludarabine, rituximab or their combinations. Cell viability was reduced from 80% to 43% in BIBB-515 (Figure 5A left) with fludarabine treatment alone; from 70% to 59% in BIBB-515 (Figure 5A middle) with rituximab treatment alone; and from 50% to 34% in BIBB-515 (Figure 5A right) with their combination treatment. The data demonstrates that BIBB-515 can lower cellular cholesterol levels, up-regulate CD-20 membrane expression and enhance cell chemoimmuno-sensitivity.
Reference: Exp Hematol Oncol. 2014 Sep 26;3:24. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4231203/
In vivo activity:
In rats and mice BIBB 515 inhibited OSC in vivo in a dose-dependent manner after 1, 3, and 5 h with ED50 values from 0.2 to 0.5 mg/kg (1 to 5 h) in rats and 0.36 (1 h) to 15.5 (3 h) and 33.3 (5 h) mg/kg in mice. Inhibition of [14C]acetate incorporation into sterols was found to parallel the effects on OSC when measured after 1 h (mice) or 3 h (rats). ED50 calculated were 0.9 mg/kg (mice) and 0.1 mg/kg (rats). Dose-dependent lipid-lowering activity was seen in normolipemic hamsters after 11 days treatment (-19% for total cholesterol and -32% for VLDL + LDL cholesterol at 55 mg/kg BIBB 515 per day) and in hyperlipemic hamsters after 25 days (-25% for total cholesterol and -59% for LDL-cholesterol at 148 mg/kg BIBB 515 per day). Calculation of kinetic parameters revealed no relevant differences between control and treatment groups in LDL clearance or fractional catabolic rates, but significant reductions of LDL production rates (-30% to -54%). Liver LDL receptor mRNA of the treated animals was not or only slightly increased. Liver VLDL secretion as measured by the Triton WR1339 method was reduced after BIBB 515 in rats and hamsters. It is concluded that the lipid-lowering effect of BIBB 515 is mainly the result of an inhibition of LDL production rather than due to an increase in LDL catabolism. OSC inhibitors may offer a novel approach for lipid-lowering therapy.
Reference: J Lipid Res. 1997 Mar;38(3):564-75. https://www.jlr.org/article/S0022-2275(20)37264-3/pdf
|
Solvent |
mg/mL |
mM |
comments |
| Solubility |
| DMSO |
1.4 |
3.62 |
|
| DMF |
0.3 |
0.79 |
|
| Ethanol |
0.2 |
0.39 |
|
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
380.87
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:
1. Benakanakere I, Johnson T, Sleightholm R, Villeda V, Arya M, Bobba R, Freter C, Huang C. Targeting cholesterol synthesis increases chemoimmuno-sensitivity in chronic lymphocytic leukemia cells. Exp Hematol Oncol. 2014 Sep 26;3:24. doi: 10.1186/2162-3619-3-24. PMID: 25401046; PMCID: PMC4231203.
2. Eisele B, Budzinski R, Müller P, Maier R, Mark M. Effects of a novel 2,3-oxidosqualene cyclase inhibitor on cholesterol biosynthesis and lipid metabolism in vivo. J Lipid Res. 1997 Mar;38(3):564-75. PMID: 9101437.
In vitro protocol:
1. Benakanakere I, Johnson T, Sleightholm R, Villeda V, Arya M, Bobba R, Freter C, Huang C. Targeting cholesterol synthesis increases chemoimmuno-sensitivity in chronic lymphocytic leukemia cells. Exp Hematol Oncol. 2014 Sep 26;3:24. doi: 10.1186/2162-3619-3-24. PMID: 25401046; PMCID: PMC4231203.
In vivo protocol:
1. Eisele B, Budzinski R, Müller P, Maier R, Mark M. Effects of a novel 2,3-oxidosqualene cyclase inhibitor on cholesterol biosynthesis and lipid metabolism in vivo. J Lipid Res. 1997 Mar;38(3):564-75. PMID: 9101437.
1: Eisele B, Budzinski R, Müller P, Maier R, Mark M. Effects of a novel 2,3-oxidosqualene cyclase inhibitor on cholesterol biosynthesis and lipid metabolism in vivo. J Lipid Res. 1997 Mar;38(3):564-75. PubMed PMID: 9101437.
2: Fouchet MH, Donche F, Martin C, Bouillot A, Junot C, Boullay AB, Potvain F, Magny SD, Coste H, Walker M, Issandou M, Dodic N. Design and evaluation of a novel series of 2,3-oxidosqualene cyclase inhibitors with low systemic exposure, relationship between pharmacokinetic properties and ocular toxicity. Bioorg Med Chem. 2008 Jun 1;16(11):6218-32. doi: 10.1016/j.bmc.2008.04.034. Epub 2008 Apr 18. PubMed PMID: 18467104.
3: Benakanakere I, Johnson T, Sleightholm R, Villeda V, Arya M, Bobba R, Freter C, Huang C. Targeting cholesterol synthesis increases chemoimmuno-sensitivity in chronic lymphocytic leukemia cells. Exp Hematol Oncol. 2014 Sep 26;3:24. doi: 10.1186/2162-3619-3-24. eCollection 2014. PubMed PMID: 25401046; PubMed Central PMCID: PMC4231203.
