LP-184 (compound 6), an acyl fluoroethylene analog, inhibits tumor growth. LP-184 has potent anti-cancer activity in ovarian, colon, prostate and pancreatic cell lines, found in patent WO2007019308A2.

Physicochemical Properties

Molecular Formula	C16H20N2O4
Molecular Weight	304.34
Exact Mass	304.142
CAS #	924835-67-6
Related CAS #	LP-284;2412580-47-1
PubChem CID	15945880
Appearance	Light yellow to yellow solid powder
LogP	-1.1
Hydrogen Bond Donor Count	3
Hydrogen Bond Acceptor Count	4
Rotatable Bond Count	2
Heavy Atom Count	22
Complexity	697
Defined Atom Stereocenter Count	1
SMILES	N(CC1C2C(=CC=1C)C(=O)[C@@](O)(C)C1(C=2C)CC1)(O)C(N)=O
InChi Key	VWMPVAZEBAKLFR-HNNXBMFYSA-N
InChi Code	InChI=1S/C16H20N2O4/c1-8-6-10-12(11(8)7-18(22)14(17)20)9(2)16(4-5-16)15(3,21)13(10)19/h6,21-22H,4-5,7H2,1-3H3,(H2,17,20)/t15-/m0/s1
Chemical Name	1-hydroxy-1-[[(5'R)-5'-hydroxy-2',5',7'-trimethyl-4'-oxospiro[cyclopropane-1,6'-indene]-1'-yl]methyl]urea
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	IC50: 0.68 μM (HT29); 0.6 μM (OVCAR-3); 16 μM (AsPC-1); 0.14 μM (PC-3)
ln Vitro	LP-184 possesses GI50s of 0.68, 0.6, 16, and 0.14 μM, which indicate its ability to suppress the development of HT29, OVCAR-3, AsPC-1, and PC-3, respectively. In the 72-hour Trypan blue assay and the 2-hour thymidine incorporation into cellular DNA assay, LP-184 exhibits anti-cancer activity with IC50s of 800 nM and 210 nM, respectively[1].
ln Vivo	LP-184 (7.5 and 10 mg/kg; ip; 21 day) provides strong 15 anti-tumor activity against MV522 tumors, resulting in 4/6 and 5/5 partial responses, in that order[1].
Animal Protocol	Animal/Disease Models: Mice (MV522 tumors )[1] Doses: 7.5 and 10 mg/kg Route of Administration: Ip; 21day Experimental Results: Effective agent for human anti-tumor therapy.
References	[1]. Illudin analogs useful as anticancer agents. WO2007019308A2.
Additional Infomation	Acylfulvene-derived Prodrug LP-184 is a tumor-site activated acylfulvene-derived prodrug and alkylating agent, with potential antineoplastic activity. Upon administration, acylfulvene-derived prodrug LP-184 becomes activated by prostaglandin reductase 1 (PTGR1), an oxidoreductase that is specifically upregulated in certain tumor cell types. The active form of LP-184 covalently binds to and alkylates DNA at N3-adenine, thereby causing double strand breaks. As tumor cells often carry DNA damage repair (DDR) mutations and are therefore deficient in DDR pathways, the DNA damage cannot be repaired. In turn, the damaged DNA causes apoptosis and inhibits proliferation in susceptible DDR mutated tumor cells. PTGR1 is often elevated in solid tumors but not in normal tissues.

Solubility Data

Solubility (In Vitro)

DMSO: 100 mg/mL (328.58 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.5 mg/mL (8.21 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 (8.21 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.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	3.2858 mL	16.4290 mL	32.8580 mL
	5 mM	0.6572 mL	3.2858 mL	6.5716 mL
	10 mM	0.3286 mL	1.6429 mL	3.2858 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.