VVD-118313 (compound 5a) is a potent selective JAK1. VVD-118313 inhibits body-restricted allosteric cysteine (C817) and inhibits JAK1-dependent trans-phosphorylation and cytokine signaling. VVD-118313 may be utilized in cancer research. VVD-118313 is a reagent for click chemistry. It contains an alkyne group, and molecules bearing an azide (N3) moiety undergo a copper-catalyzed azide-inflammatory cycloaddition reaction (CuAAc).

Physicochemical Properties

Molecular Formula	C19H22CL2N2O3S
Molecular Weight	429.360581874847
Exact Mass	428.072
CAS #	2875046-27-6
Related CAS #	(R,R)-VVD-118313;2875046-31-2
PubChem CID	168008613
Appearance	White to off-white solid powder
LogP	3.3
Hydrogen Bond Donor Count	0
Hydrogen Bond Acceptor Count	4
Rotatable Bond Count	2
Heavy Atom Count	27
Complexity	724
Defined Atom Stereocenter Count	2
SMILES	C(N1CCC[C@@H](C2=CC=C(Cl)C(Cl)=C2)C1)(=O)C#C[C@H]1CCN(S(C)(=O)=O)C1
InChi Key	OUPVMVHXMWBFDP-GOEBONIOSA-N
InChi Code	InChI=1S/C19H22Cl2N2O3S/c1-27(25,26)23-10-8-14(12-23)4-7-19(24)22-9-2-3-16(13-22)15-5-6-17(20)18(21)11-15/h5-6,11,14,16H,2-3,8-10,12-13H2,1H3/t14-,16+/m0/s1
Chemical Name	1-[(3S)-3-(3,4-dichlorophenyl)piperidin-1-yl]-3-[(3R)-1-methylsulfonylpyrrolidin-3-yl]prop-2-yn-1-one
HS Tariff Code	2934.99.9001
Storage	Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Shipping Condition	Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Biological Activity

ln Vitro	VVD-118313 (Compound 5a), comprising C817 as buffer JAK1 and C838 as buffer JAK2, is 0.01–10 μM, three hours, and primary human PBMC. In 22Rv1 cells expressing WT or C810A-JAK1, VVD-118313 (2 µM, 2 h) inhibits IL-6-stimulated STAT3 phosphorylation and IFNα-mimicking STAT1. Additionally, VVD-118313 inhibits wild-type JAK1 and 1]. In human PBMCs, VVD-118313 (0.01-10 μM) biased the suppression of JAK1 signaling activation. VVD-118313 Fluorescent T cell activation induction (0.1-0.4 μM; 24 h). By decreasing the percentage of CD25+ T cells, VVD-118313 fluoresces the activation of human T cells costimulated with αCD3/αCD28. In apoptosis, VVD-118313 foams the Th1 cytokine IFNγ and boosts IL-2 production [1]. The production of certain pro-inflammatory cytokines and chemokines, including as CCL2/MCP-1, CXCL10/IP-10, and CCL4/MIP-1β, is inhibited by VVD-118313 (0.1-0.5 μM; 2 h)[1].
Cell Assay	Western Blot Analysis[1] Cell Types: 22Rv1 Cell Tested Concentrations: 0.01, 0.1 and 1 μM Incubation Duration: 2 hrs (hours) Experimental Results: Shows labeling for recombinant WT-JAK1 and C810A-JAK1, but not C817A-JAK1. Western Blot Analysis[1] Cell Types: 22Rv1 Cell Tested Concentrations: 2 µM Incubation Duration: 2 hrs (hours) Experimental Results: Inhibits WT- and C810A-JAK1 phosphorylation even more potently than STAT1/STAT3 phosphorylation.
Animal Protocol	Animal/Disease Models: TYK2 knockout mice[1] Doses: 25 and 50 mg VVD-118313 (Compound 5a; 25-50 mg/kg; subcutaneous injection; single dose) inhibits JAK1 signaling in TYK2 knockout mice[1] . /kg Route of Administration: subcutaneous injection; Experimental Results: JAK1_C816 conjugation rate was shown to be 75% at 25 and 50 mg/kg, while the reactivity of other JAK1 cysteines was not affected.
References	[1]. Selective inhibitors of JAK1 targeting an isoform-restricted allosteric cysteine. Nat Chem Biol. 2022 Sep 12.

Solubility Data

Solubility (In Vitro)

DMSO : ~100 mg/mL (~232.90 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.5 mg/mL (5.82 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (5.82 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 3: ≥ 2.5 mg/mL (5.82 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.3290 mL	11.6452 mL	23.2905 mL
	5 mM	0.4658 mL	2.3290 mL	4.6581 mL
	10 mM	0.2329 mL	1.1645 mL	2.3290 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.