CAM833 is a potent orthotopic inhibitor of the interaction between BRCA2 and RAD51, with a Kd of 366 nM for ChimRAD51 protein. CAM833 also inhibits RAD51 oligomerization. CAM833 promotes the apoptosis process of G2/M-arrested cells.

Physicochemical Properties

Molecular Formula	C26H26CLFN4O5
Molecular Weight	528.959848880768
Exact Mass	528.157
CAS #	2758364-02-0
PubChem CID	155387716
Appearance	White to off-white solid powder
LogP	2.8
Hydrogen Bond Donor Count	3
Hydrogen Bond Acceptor Count	7
Rotatable Bond Count	7
Heavy Atom Count	37
Complexity	837
Defined Atom Stereocenter Count	3
SMILES	ClC1C=C(C=CC=1[C@H](C)NC([C@@H]1C[C@H](CN1C(CNC(C1C=CC2C=C(C=CC=2N=1)F)=O)=O)O)=O)OC
InChi Key	PMUWBFKMLGLUTF-KNUWZQJKSA-N
InChi Code	InChI=1S/C26H26ClFN4O5/c1-14(19-6-5-18(37-2)11-20(19)27)30-26(36)23-10-17(33)13-32(23)24(34)12-29-25(35)22-7-3-15-9-16(28)4-8-21(15)31-22/h3-9,11,14,17,23,33H,10,12-13H2,1-2H3,(H,29,35)(H,30,36)/t14-,17+,23-/m0/s1
Chemical Name	N-[2-[(2S,4R)-2-[[(1S)-1-(2-chloro-4-methoxyphenyl)ethyl]carbamoyl]-4-hydroxypyrrolidin-1-yl]-2-oxoethyl]-6-fluoroquinoline-2-carboxamide
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

Targets	Kd: 355 nM (ChimRAD51, measured by FP), 366 nM (ChimRAD51, measured by ITC)[1]
ln Vitro	CAM833 (3.125-50 μM; 24 h) causes RAD51 foci to diminish in concentration-dependent fashion, which in turn induces an increase in DNA damage [1]. RAD51 molecular clustering at DNA damage sites and the synthesis of extended RAD51 microfilaments are inhibited by CAM833 (25 μM) [1]. Through homologous recombination, CAM833 (0–50 μM) prevents DNA repair [1]. Over time, CAM833 (20 μM; 0-72 h) boosts apoptosis in HCT116 cells and improves radiation-induced cell cycle arrest [1]. In human cell lines generated from different malignancies, CAM833 (0.1-100 μM; 96 h) exhibits dose-dependent growth suppression; this inhibition is exacerbated when coupled with ionizing radiation [1]. The growth inhibitory impact of PARP1 inhibition in BRCA2 wild-type cells is enhanced by CAM833 (20 μM; 96 h) [1]. With a GI50 (50% growth inhibition) of 38 μM, CAM833 (96 h) on its own suppresses the growth of HCT116 colon cancer cells. CAM833 has a GI50 of 14 μM and suppresses the proliferation of HCT116 colon cancer cells when coupled with 3 Gy IR [1]. The methyl substituted α-methylbenzyl methyl group resides in the Ala binding pocket on RAD51, while the quinoline on CAM833 occupies the Phe binding pocket [1].
Cell Assay	Cell Cycle Analysis[1] Cell Types: HCT116 cells Tested Concentrations: 20 μM Incubation Duration: 0-72 h Experimental Results: In the control the percentage of cells in the apoptotic subG1 fraction remains below 5% throughout, in the compound-treated cells this rises progressively to peak at 15% at 48 hrs (hours).
References	[1]. A small-molecule inhibitor of the BRCA2-RAD51 interaction modulates RAD51 assembly and potentiates DNA damage-induced cell death. Cell Chem Biol. 2021 Jun 17;28(6):835-847.e5.

Solubility Data

Solubility (In Vitro)

DMSO : 125 mg/mL (236.31 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	1.8905 mL	9.4525 mL	18.9050 mL
	5 mM	0.3781 mL	1.8905 mL	3.7810 mL
	10 mM	0.1891 mL	0.9453 mL	1.8905 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.