(R,R)-VVD-118313 is the seven bodies of VVD-118313. VVD-118313 is a selective JAK1 inhibitor that can suppress JAK1-dependent trans-phosphorylation and cytokine signaling. VVD-118313 may be used in cancer research. (R,R)-VVD-118313 is a reagent for click chemistry. It contains an alkyne group and can undergo copper-catalyzed azide-initiated cycloaddition (CuAAc) with compounds bearing an Azide group.

Physicochemical Properties

Molecular Formula	C19H22CL2N2O3S
Molecular Weight	429.36
Exact Mass	428.072
CAS #	2875046-31-2
Related CAS #	VVD-118313;2875046-27-6
PubChem CID	168446364
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](C2C=CC(=C(C=2)Cl)Cl)C1)(=O)C#C[C@H]1CCN(C1)S(=O)(=O)C
InChi Key	OUPVMVHXMWBFDP-HOCLYGCPSA-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-[(3R)-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].
ln Vivo	VVD-118313 (Compound 5a; 25-50 mg/kg; subcutaneous injection; single dosage) suppresses JAK1 signaling in TYK2 knockout mice [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. Inhibits WT- and C810A-JAK1 phosphorylation even more potently than STAT1/STAT3 phosphorylation.
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)

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples. Injection Formulations (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] *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. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Oral Formulations Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.  (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.