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NVP-AUY954 is an orally-available, benzothiazole-based, monoselective agonist of the sphingosine-1-

phosphate receptor 1 (S1P1) intended for the treatment of human autoimmune mediated inflammatory

neuropathies. Along with EC50 potency of 1.2 nM, NVP-AUY954 has at least 280-fold selectivity for S1P1

compared to the receptor's four other subtypes.

NVP-AUY954 induces a potent and reversible reduction of circulating lymphocytes; in combination with

Everolimus, NVP-AUY954 can prolong the survival of cardiac allografts in a rat transplantation model. NVP-

AUY954 also has been shown to activate downstream kinase cascades, increasing Erk (Tyr204) and Akt

(Ser473) phosphorylation at EC50s of 0.1 and 1.0 nM, respectively.

NVP-AUY954 efficacy has been correlated with an accumulation of plasmacytoid dendritic cells (pDC), which

may have therapeutic value in the treatment of multiple sclerosis.

Chemical Formula:

C₂₅H₂₀F₃NO₂S

CAS No.:

N/A

Molecular Weight:

455.12

Purity:

> 99%

Appearance:

White

Chemical Name:

3-[[2-[4-phenyl-3-(trifluoromethyl)phenyl]-1-benzothiophen-5-yl]methylamino]

propanoic acid

Solubility:

Up to 50 mM in DMSO

Synonyms:

NVP-AUY954, AUY954, AUY-954

Storage:

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

at -20^oC.

Reference:

1. Zhang et al., AUY954, a selective S1P1 modulator, prevents experimental autoimmune neuritis. J.

Neuroimmunol. 2009, 216, 59-65.

2. Pan et al., A Monoselective Sphingosine-1-Phosphate Receptor-1 Agonist Prevents Allograft Rejection in a

Stringent Rat Heart Transplantation Model. Chem. Biol. 2006, 13, 1227-1234.

3. Galicia-Rosas et al., A Sphingosine-1-Phosphate Receptor 1-Directed Agonist Reduces Central Nervous

System Inflammation in a Plasmacytoid Dendritic Cell-Dependent Manner. J. Immunol. 2012, 189, 3700-3706.

PHA-793887 is an intravenously-administered, inhibitor of cyclin dependent kinases CDK2, CDK5, CDK7, at

IC50s of 8 nM, 5 nM, and 10 nM, respectively. [1] As a multi-CDK isoform inhibitor, it was postulated that

PHA-793887 might overcome resistance-based mechanisms and lead to enhanced tumor suppression. PHA-

793881 was found in Phase I dose-ranging studies to induce severe dose-related hepatotoxicity, thus halting

clinical studies.

Additionally, PHA-793887 was found to impair TLR signaling, thus suppressing cytokine production (type 1

interferon, interleukin-6, -10, -12, and TNFa), thereby increasing susceptibility of cancer patients to diseases

such as herpes viridae. [3]

PHA-793887 was found to be an effective tool compound for the monitoring of the E2F gene signature

pathway.

Chemical Formula:

C₁₉H₃₁N₅O₂

CAS No.:

718630-59-2

Molecular Weight:

361.48

Purity:

> 98%

Appearance:

Off White

Chemical Name:

N-(6,6-dimethyl-5-(1-methylpiperidine-4-carbonyl)-1,4,5,6-tetrahydropyrrolo[3,4-c]

pyrazol-3-yl)-3-methylbutanamide

Solubility:

Up to 100 mM in DMSO

Synonyms:

PHA-793887, PHA 793887, PHA793887

Storage:

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

at -20^oC.

Reference:

1. Brasca et al. Optimization of 6,6-dimethyl pyrrolo[3,4-c]pyrazoles: Identification of PHA-793887, a potent

   CDK inhibitor suitable for intravenous dosing. Bioorg Med Chem, 2010, 18(5), 1844-1853.

2. Massard et al., A first in man, phase I dose-escalation study of PHA-793887, an inhibitor of multiple cyclin-

   dependent kinases (CDK2, 1 and 4) reveals unexpected hepatotoxicity in patients with solid tumors. Cell

   Cycle 2011, 10(6), 963-970.

3.Zoubir et al., An inhibitor of cyclin-dependent kinases suppresses TLR signaling and increases the

  susceptibility of cancer patients to herpesviridae. Cell Cycle 2011, 10(1), 118-126.

4.Locatelli et al., Transcriptional analysis of an E2F gene signature as a biomarker of activity of the cyclin-

  dependent kinase inhibitor PHA-793887 in tumor and skin biopsies from a phase I clinical study. Mol.   

  Cancer Ther. 2010, 9(5), 1265-1273

R788 is an orally-available, ATP-competitive, methylene phosphate prodrug of R406, which is a potent

inhibitor of Syk (IC50 = 41 nM). [1] In a broad panel of receptor, ion channel, and enzyme binding assays,

R406 was shown to inhibit adenosine A3 receptor (IC50 = 81 nM), adenosine transporter (IC50 = 1.8 uM), and

monoamine transporter (IC50 = 2.7 uM). Followup measurements for ligand-induced guanosine 5'-O-

(thiotriphosphate) binding to the adenosine A3 receptor showed that R406 possesses antagonistic activity

with an IC50 of 93 nM. R406 inhibits phosphorylation of Syk substrate linker for activation of T cells in mast

cells and B-cell linker protein/SLP65 in B cells. R406 does not inhibit phosphorylation of Sky tyrosine 352, but

does inhibit phosphorylation of LAT tyrosine 191. R406 also inhibits IgE- and IgG-mediated activation of Fc

receptor signaling.

In a large panel of diffuse large B-cell lymphoma cell lines, R406 inhibited cellular proliferation at EC50s

ranging from 0.8 to 8.1 uM.

Chemical Formula:

C₂₃H₂₄FN₆O₉P.2Na

CAS No.:

1025687-58-4

Molecular Weight:

624.42

Purity:

> 98%

Appearance:

White

Chemical Name:

2H-Pyrido[3,2-b]-1,4-oxazin-3(4H)-one, 6-[[5-fluoro-2-[(3,4,5-trimethoxyphenyl)

amino]-4-pyrimidinyl]amino]-2,2-dimethyl-4-[(phosphonooxy)methyl]-, sodium

salt (1:2)

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.

Reference:

1. Braselmann S., et al. R406, an orally available spleen tyrosine kinase inhibitor blocks fc receptor signaling

   and reduces immune complex-mediated inflammation. J Pharmacol Exp Ther. 2006; 319(3):998-1008.

2. Sweeny DJ, Li W, Grossbard E, Lau DT. Contribution of gut bacteria to the metabolism of the spleen

    tyrosine kinase (Syk) inhibitor R406 in cynomolgus monkey. Xenobiotica. 2010;40(6):415-23.

Leukadherin-1 (LA1), a novel small molecule agonist of integrin CD11b/CD18, can increase the extent of

CD11b/CD18-dependent cell adhesion of transfected cells and of primary human and mouse neutrophils

(EC50 =4µM in vitro), which resulted in decreased chemotaxis and transendothelial migration. LA1 can also

decrease leukocyte recruitment and reduced arterial narrowing after injury in rats. Moreover, compared to a

known integrin antagonist, LA1 preserved kidney function better in a mouse model of experimental nephritis.

It inhibited leukocyte recruitment by increasing leukocyte adhesion to the inflamed endothelium, which was

reversed with a blocking antibody.

Chemical Formula:

C₂₂H₁₅NO₄S₂

CAS No.:

344897-95-6

Molecular Weight:

421.49

Purity:

> 98%

Appearance:

White solid

Chemical Name:

(Z)-4-(5-((3-benzyl-4-oxo-2-thioxothiazolidin-5-ylidene)methyl)furan-2-yl)benzoic acid

Solubility:

Up to 50 mM in DMSO

Synonyms:

Fostamatinib disodium, Fostamatinib, R788, R935788

Storage:

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

at -20^oC.

Reference:

1. Braselmann et al., R406, an orally available spleen tyrosine kinase inhibitor blocks fc receptor signaling

   and reduces immune complex-mediated inflammation. J. Pharma. Exp. Ther. 2006, 319(3), 998-1008.

2. Chen et al., SYK-dependent tonic B-cell receptor signaling is a rational treatment target in diffuse large B-

    cell lymphoma. Blood 2008, 111, 2230-2237. Pubmed ID: 18006696