Cloxacillin Sodium hydrate (HSDB-3042), a semi-synthetic and chlorinated derivative of Oxacillin, is a potent and orally bioactive antibacterial agent acting as a β-lactamase inhibitor with an IC50 of 0.04 µM. Cloxacillin can suppress the S. aureus-induced inflammatory response by inhibiting the activation of MAPKs, NF-кB and NLRP3-related protein.

Physicochemical Properties

Molecular Formula	C19H17CLN3NAO5S
Molecular Weight	457.8632
Exact Mass	457.047
Elemental Analysis	C, 49.84; H, 3.74; Cl, 7.74; N, 9.18; Na, 5.02; O, 17.47; S, 7.00
CAS #	7081-44-9
Related CAS #	Cloxacillin sodium;642-78-4;Cloxacillin;61-72-3
PubChem CID	23675320
Appearance	White to light yellow solid powder.
Boiling Point	689.7ºC at 760 mmHg
Flash Point	370.9ºC
LogP	0.992
Hydrogen Bond Donor Count	1
Hydrogen Bond Acceptor Count	7
Rotatable Bond Count	4
Heavy Atom Count	30
Complexity	728
Defined Atom Stereocenter Count	3
SMILES	ClC1=C([H])C([H])=C([H])C([H])=C1C1C(=C(C([H])([H])[H])ON=1)C(N([H])[C@]1([H])C(N2[C@@]([H])(C(=O)[O-])C(C([H])([H])[H])(C([H])([H])[H])S[C@@]21[H])=O)=O.[Na+]
InChi Key	InChI=1S/C19H18ClN3O5S.Na/c1-8-11(12(22-28-8)9-6-4-5-7-10(9)20)15(24)21-13-16(25)23-14(18(26)27)19(2,3)29-17(13)23;/h4-7,13-14,17H,1-3H3,(H,21,24)(H,26,27);/q;+1/p-1/t13-,14+,17-;/m1./s1
InChi Code	InChI=1S/C19H18ClN3O5S.Na/c1-8-11(12(22-28-8)9-6-4-5-7-10(9)20)15(24)21-13-16(25)23-14(18(26)27)19(2,3)29-17(13)23;/h4-7,13-14,17H,1-3H3,(H,21,24)(H,26,27);/q;+1/p-1/t13-,14+,17-;/m1./s1
Chemical Name	sodium (2S,5R,6R)-6-(3-(2-chlorophenyl)-5-methylisoxazole-4-carboxamido)-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylate
Synonyms	Cloxacilina; Cloxacilline; Cloxacillinum; Syntarpen; Tegopen, Cloxacillin sodium.
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 Note: (1). This product requires protection from light (avoid light exposure) during transportation and storage.(2). Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture.
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

Targets	Tetracycline
ln Vitro	For S. aureus 8325-4 and DU1090, cloxacillin sodium monohydrate (0–2048 µg/mL; 20–24 h) exhibits good antibacterial activity with MIC values of 0.125 µg/mL[1]. The hemolytic activity of Hlα is inhibited in vitro by cloxacillin sodium monohydrate (0.015625 μg/mL; 6 h). This inhibition is enhanced when combined with TZ and TZ. Additionally, cloxacillin sodium monohydrate suppresses the inflammatory response by preventing the activation of MAPKs, NF-кB, and NLRP3-related proteins[1].
ln Vivo	Cloxacillin (HSDB-3042) (1.6125 mg/kg; s.c.; 12-h intervals for 72 h) protects mice from S. aureus peritonitis in vivo when combines with Thioridazine and Tetracycline[1]. Cloxacillin (7.5 mg/per; i.p.; twice daily from day 3 for 3 days) develops less severe synovitis and reduces bone erosions when combines with anti-IL-15 antibodies[3]. Animal Model: Female BALB/c mice (6-week-old; peritonitis model)[1]. Dosage: 1.6125 mg/kg (combines with TC (3.125 mg/kg) and TZ (25 mg/kg)) Administration: Subcutaneous injection; 12-h intervals for 72 h. Result: Reduced the degree of inflammatory cell infiltration in the mouse lung tissue and alveolar structures tended to be normal. Significantly reduced the pathological changes in spleen and liver tissue, as well as decreased the CFU counts of S. aureus in the peritoneal cavity. Animal Model: Female wildtype C57BL/6 mice (8-week-old; systemic S. aureus-induced arthritis model) Dosage: 7.5 mg/per (combines with 25 µg/per anti-IL-15 antibodies) Administration: Intraperitoneal injection; twice daily from day 3 (after bacterial inoculation) and stopped at day 6. Result: Showed activities of reducing severe synovitis and bone erosions when combined with anti-IL-15 antibodies.
Cell Assay	Cell Line: S. aureus 8325-4, S. aureus DU1090 (an Hlα-deleted strain) Concentration: 0-2048 µg/mL Incubation Time: 20-24 h Result: inhibited DU1090 and S. aureus 8325-4 with MIC values of 0.125 µg/mL.
Animal Protocol	Animal Model: Eight weeks old; systemic S. aureus-induced arthritis model; female wildtype C57BL/6 mice) Dosage: 7.5 mg/per (combines with 25 µg/per anti-IL-15 antibodies) Administration: intraperitoneal injection; started on day 3 (following bacterial inoculation) and continued every day until day 6. Result: demonstrated effects on bone erosions and severe synovitis when paired with anti-IL-15 antibodies.
References	[1]. The combination of cloxacillin, thioridazine and tetracycline protects mice against Staphylococcus aureus peritonitis by inhibiting α-Hemolysin-induced MAPK/NF-κB/NLRP3 activation. Int J Biol Macromol. 2022 Feb 15;198:1-10. [2]. Antibiotics with Interleukin-15 Inhibition Reduce Joint Inflammation and Bone Erosions but Not Cartilage Destruction in Staphylococcus aureus-Induced Arthritis. Infect Immun. 2018 Apr 23;86(5):e00960-17. [3]. Group 1 beta-lactamases of Aeromonas caviae and their resistance to beta-lactam antibiotics. Can J Microbiol. 2003 Mar;49(3):207-15.
Additional Infomation	Cloxacillin sodium is an organic sodium salt. It contains a cloxacillin(1-). Cloxacillin Sodium is the sodium salt of cloxaclliin, a semisynthetic beta-lactamase resistant penicillin antibiotic with antibacterial activity. Cloxacillin binds to and inactivates penicillin-binding proteins (PBPs) located on the inner membrane of the bacterial cell wall, thereby preventing the cross-linkage of peptidoglycans, which are critical components of the bacterial cell wall. This leads to an interruption of the bacterial cell wall and causes bacterial cell lysis. Cloxacillin Sodium Anhydrous is the anhydrous form of the sodium salt of cloxacillin, a semisynthetic beta-lactamase resistant penicillin antibiotic with antibacterial activity. Cloxacillin binds to and inactivates penicillin-binding proteins (PBPs) located on the inner membrane of the bacterial cell wall, thereby preventing the cross-linkage of peptidoglycans, which are critical components of the bacterial cell wall. This leads to an interruption of the bacterial cell wall and causes bacterial cell lysis. A semi-synthetic antibiotic that is a chlorinated derivative of OXACILLIN. See also: Cloxacillin (has active moiety).

Solubility Data

Solubility (In Vitro)

DMSO : 55~100 mg/mL (115.57~210.14 mM ) Ethanol : ~25 mg/mL H2O : ~50 mg/mL (~105.07 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.5 mg/mL (5.25 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 (5.25 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 (5.25 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. Solubility in Formulation 4: 10% DMSO+40% PEG300+5% Tween-80+45% Saline: ≥ 2.5 mg/mL (5.25 mM) Solubility in Formulation 5: 100 mg/mL (210.14 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.1841 mL	10.9204 mL	21.8407 mL
	5 mM	0.4368 mL	2.1841 mL	4.3681 mL
	10 mM	0.2184 mL	1.0920 mL	2.1841 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.