Products

Dalcetrapib (JTT-705) is a CETP inhibitor of the thioaniline family with a potency of 0.2 uM aimed at raising

HDL cholesterol levels. It also inhibits CETP-mediated transfer of CE from HDL to apoB-containing

lipoproteins in human plasma at an IC50 of 9 uM. [1] Dalcetrapib is the first molecule that both regulates

CETP and demonstrates an anti-atherogenic effect in vivo. [1] It differs from anacetrapib by binding to a

different site on CETP, uniquely inducing a conformational change in the CETP molecule which correlates

with reduced CETP activity in humans.

Early clinical studies have shown a 26-28% increase in HDL with 600 mg qd dosing. [2] Phase II trials

demonstrated that CETP activity was reduced by 50% and HDL levels increased as much as 31%, while LDL

levels were unchanged.

Despite halting development in May, 2012, Dalcetrapib remains as a valuable benchmarking tool compound

in vitro for modulation of HDL cholesterol levels.

Chemical Formula:

C₂₃H₃₅NO₂S

CAS No.:

211513-37-0

Molecular Weight:

389.59

Purity:

> 98%

Appearance:

Light Yellow

Chemical Name:

S-2-(1-(2-ethylbutyl)cyclohexanecarboxamido)phenyl 2-methylpropanethioate

Solubility:

Up to 100 mM in DMSO

Synonyms:

JTT-705, JTT705, Dalcetrapib, RO4607381

Storage:

For longer shelf life, store solid powder at 4^oC desiccated, or store DMSO solution

at -20^oC.

References:

1. Shinkai, H., Cholesteryl ester transfer-protein modulator and inhibitors and their potential for the treatment

   of cardiovascular diseases. Vascular Health and Risk Management, 2012, 8, 323-331.

2. Goldberg et al., Cholesteryl ester transfer protein inhibitors for dyslipidemia: focus on dalcetrapib. Drug

    Design, Development, and Therapy, 2012, 6, 251-259.

3. Durrington, Br. J. Cardiol. 2012, 19(3), 126-133

LY-2484595 (Evacetrapib) is a benzazepine-based, selective inhibitor of cholesteryl ester transfer protein

(CETP) at an IC50 value of 5.5 nM for human recombinant CETP. Inhibition in human plasma was 3.6 nM

IC50. [1] In H295R cells at concentrations up to 10 uM, LY-2484595 has been shown to elevate HDL

cholesterol without inducing aldosterone, cortisol synthesis, or increasing blood pressure.

In a randomized controlled trial of 398 patients with elevated LDL and low HDL, LY-2484595 was shown to be

effective in lowering LDL and raising HDL. In combination with statins, LY-2484595 showed greater efficacy in

lowering LDL with no adverse effects.

Chemical Formula:

C₃₁H₃₆F₆N₆O₂

CAS No.:

1186486-62-3

Molecular Weight:

638.65

Purity:

> 98%

Appearance:

White Crystalline

Chemical Name:

Trans-4-({(5S)-5-[{[3,5-bis(trifluoromethyl)phenyl]methyl}(2-methyl-2H-tetrazol-5- yl)

amino]-7,9-dimethyl-2,3,4,5-tetrahydro-1H-benzazepin-1-yl}methyl)

cyclohexanecarboxylic acid

Solubility:

Up to 22 mM in DMSO

Synonyms:

LY-2484595, LY 2484595, LY2484595, Evacetrapib

Storage:

For longer shelf life, store solid powder at 4^oC desiccated, or store DMSO solution

at -20^oC.

References:

1. Cao et al., Evacetrapib is a novel, potent, and selective inhibitor of cholesteryl ester transfer protein that

   elevates HDL cholesterol without inducing aldosterone or increasing blood pressure. J. Lipid Res. 2011, 52,

   2169-2176.

2. Nicholls et al., Effects of the CETP inhibitor evacetrapib administered as monotherapy or in combination

   with statins on HDL and LDL cholesterol: a randomized controlled trial. JAMA 2011, 306(19), 2099-2109.

SD169 is an indole-5-carboxamide, orally-available, ATP-competitive, a-selective p38 MAPK inhibitor that

targets a wide variety of inflammatory cells, including neutrophils, monocytes, macrophages, B and CD4+ T

cells, and endothelial cells. [1] Through interactions with Schwann cell and TNF activity, SD169 promotes

axonal regeneration in peripheral nerves. [2]

SD169 has been shown to reduce myeloma-induced osteolytic bone lesions and restored bone mass by

downregulating osteoclastogenesis and osteoblastogenesis in xenografted primary myeloma-SCID-hu or

myeloma cell line-SCID mouse models. [3] SD169 was also shown downregulates pp38 in myeloma cells in

vitro and in vivo.

in the diabetes therapeutic area, SD169 significantly reduces p38 and HSP60 expression in T cells of the

pancreatic beta islets. In studies using hyperglycemic NOD mice, SD169 treatment lowered blood glucose

and improved glucose homeostasis. [4]

Chemical Formula:

C₉H₈N₂O

CAS No.:

1670-87-7

Molecular Weight:

160.17

Purity:

> 98%

Appearance:

White

Chemical Name:

1H-indole-5-carboxamide

Solubility:

Up to 22 mM in DMSO

Synonyms:

SD-169, SD169

Storage:

For longer shelf life, store solid powder at 4^oC desiccated, or store DMSO solution

at -20^oC.

References:

1. Medicherla et al., p38 MAPK inhibition reduces diabetes-induced impairment of wound healing. Diabetes,

   Metab. Syndr. Obes. 2009, 2, 91-100.

2. Myers et al., Inhibition of p38 MAP kinase activity enhances axonal regeneration. Exp. Neurol. 2003, 184,

   606-614.

3. Yang et al., Constitutive activation of p38 MAPK in tumor cells contributes to osteolytic bone lesions in

    multiple myeloma. Leukemia, 2012, 26, 2114-2123.

4. Medicherla et al., J. Pharmacol. Exp. Ther. 2006, 318(1), 99-107.

Sitagliptin (also named MK-0431 and marketed as Januvia) is a competitive inhibitor of the enzyme dipeptidyl

peptidase 4 (DPP-4). Sitagliptin can increase incretin levels (GLP-1 and GIP), which inhibit glucagon

release, which in turn increases insulin secretion, decreases gastric emptying, and decreases blood

glucose levels.

Chemical Formula:

C₁₆H₁₅F₆N₅O

CAS No.:

486460-32-6

Molecular Weight:

407.31

Purity:

> 98%

Appearance:

White solid

Chemical Name:

(3R)-3-Amino-1-[3-(trifluoromethyl)-5,6,7,8-tetrahydro-1,2,4-triazolo[4,3-a]pyrazin-7-

yl]-4-(2,4,5-trifluorophenyl)butan-1-one

Solubility:

Up to 100 mM in DMSO

Storage:

For longer shelf life, store solid powder at 4^oC desiccated, or store DMSO solution

at -20^oC.

References:

1. Herman GA, et al.Pharmacokinetics and pharmacodynamics of sitagliptin, an inhibitor of dipeptidyl

   peptidase IV, in healthy subjects: results from two randomized, double-blind, placebo-controlled studies

   with single oral doses. Clin Pharmacol Ther 2005; 78 (6): 675–88.

2. Herman GA, et al. Pharmacokinetics and pharmacodynamic effects of the oral DPP-4 inhibitor sitagliptin

   in middle-aged obese subjects. J Clin Pharmacol 2006;46 (8): 876–86.

3. Lee B, et al. Pharmacokinetic, pharmacodynamic, and efficacy profiles of alogliptin, a novel inhibitor of

   dipeptidyl peptidase-4, in rats, dogs, and monkeys. Eur J Pharmacol. 2008;589(1-3):306-14