Physicochemical Properties
| Molecular Formula | C10H16BR2N2O2 |
| Molecular Weight | 356.05 |
| Exact Mass | 353.958 |
| Elemental Analysis | C, 33.73; H, 4.53; Br, 44.88; N, 7.87; O, 8.99 |
| CAS # | 54-91-1 |
| PubChem CID | 4842 |
| Appearance | White to off-white solid powder |
| Density | 1.691g/cm3 |
| Boiling Point | 487.1ºC at 760mmHg |
| Melting Point | 106-107ºC |
| Flash Point | 248.4ºC |
| Index of Refraction | 1.566 |
| LogP | 1.103 |
| Hydrogen Bond Donor Count | 0 |
| Hydrogen Bond Acceptor Count | 2 |
| Rotatable Bond Count | 4 |
| Heavy Atom Count | 16 |
| Complexity | 227 |
| Defined Atom Stereocenter Count | 0 |
| SMILES | O=C(N1CCN(C(CCBr)=O)CC1)CCBr |
| InChi Key | NJBFOOCLYDNZJN-UHFFFAOYSA-N |
| InChi Code | InChI=1S/C10H16Br2N2O2/c11-3-1-9(15)13-5-7-14(8-6-13)10(16)2-4-12/h1-8H2 |
| Chemical Name | 3-bromo-1-[4-(3-bromopropanoyl)piperazin-1-yl]propan-1-one |
| Synonyms | Pipobroman; NSC25154; Trade names Vercite Vercyte |
| 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
| ADME/Pharmacokinetics |
Absorption, Distribution and Excretion Well absorbed from the GI tract. The drug is well absorbed following oral administration. Studies of its distribution and fate in man have not been reported. |
| References |
[1]. Treatment of polycythemia vera with hydroxyurea and pipobroman: final results of a randomized trial initiated in 1980. J Clin Oncol. 2011 Oct 10;29(29):3907-13. [2]. Association of Vemurafenib and Pipobroman Enhances BRAF-CRAF Dimerization in Squamous Cell Carcinoma. J Invest Dermatol. 2016 Jun;136(6):1302-1305. |
| Additional Infomation |
Pipobroman can cause developmental toxicity according to state or federal government labeling requirements. Pipobroman is an N-acylpiperazine that is piperazine in which each of the nitrogens has been acylated by a 3-bromopropionoyl group. An anti-cancer drug. It has a role as an antineoplastic agent and an alkylating agent. It is a N-acylpiperazine, a tertiary carboxamide and an organobromine compound. An antineoplastic agent that acts by alkylation. Pipobroman has been reported in Bos taurus with data available. Pipobroman is a piperazine derivative with potential antineoplastic alkyating activity. Although the exact mechanism of action of pipobroman has yet to be fully elucidated, this agent appears to act by alkylating DNA, leading to disruption of DNA replication and eventually cell death. An antineoplastic agent that acts by alkylation. Drug Indication For the treatment of polycythaemia vera and refractory chronic myeloid leukaemia. Mechanism of Action The mechanism of action is uncertain, but due to the structural similarity with other DNA alkylating agents, pipobroman is thought to alkylate DNA leading to disruption of DNA synthesis and eventual cell death. Pipobroman has been classified as a polyfunctional alkylating agent, but its precise mechanism of action is not known. Therapeutic Uses Antineoplastic Agents, Alkylating ...ANTINEOPLASTIC DRUG OF ALKYLATING TYPE. @ PRESENT ITS USE IS MAINLY LIMITED TO TREATMENT OF POLYCYTHEMIA VERA & CHRONIC GRANULOCYTIC LEUKEMIA. EVEN IN THESE DISORDERS...PIPOBROMAN IS GENERALLY NOT AS EFFECTIVE AS OLDER MODES OF TREATMENT. ...PIPOBROMAN IS HELD IN RESERVE FOR USE IN PATIENTS THAT HAVE BECOME REFRACTORY TO X-IRRADIATION & BUSULFAN IN CASE OF LEUKEMIA & PHLEBOTOMY & RADIOPHOSPHATE IN CASE OF POLYCYTHEMIA VERA. Pipobroman is indicated mainly in the treatment of polycythemia vera. In the limited number of studies reported, there seems to be no difference in the therapeutic response between patients who had been under prior treatment with other drugs and those who had not. There are insufficient data available to provide a comparison of the effectiveness of pipobroman with conventional forms of treatment (radioactive phosphorus, phlebotomy, or other alkylating agents); however, it may be effective in patients with polycythemia vera who are refractory to these forms of therapy. Although pipobroman has produced remission in chronic myelocytic (granulocytic) leukemia, the number of reported cases is too few to permit evaluation of the drug for this condition and its use is therefore reserved for patients whose disease is resistant to other therapy. Drug Warnings PATIENTS IN WHOM BONE MARROW FUNCTION IS STILL DEPRESSED FROM PREVIOUS IRRADIATION OR OTHER CYTOTOXIC CHEMOTHERAPY SHOULD NOT RECEIVE PIPOBROMAN. CLINICAL EXPERIENCE WITH THIS DRUG IS INSUFFICIENT TO RECOMMEND ITS USE IN CHILDREN UNDER 15 YR OF AGE. PIPOBROMAN...SHOULD NOT BE ADMIN DURING PREGNANCY, SINCE THERE IS NO INFORMATION ON ITS POTENTIAL TERATOGENICITY. Rash and adverse GI effects such as nausea, vomiting, abdominal cramping, diarrhea, and anorexia may occur. These adverse effects are usually transient, but may persist and necessitate cessation of therapy. Pipobroman should not be administered to patients with bone marrow depression resulting from radiation therapy or cytotoxic chemotherapy. Pharmacodynamics Pipobroman is an antineoplastic agent. Specifically, it is a piperazine derivative with a chemical structure close to that of many DNA alkylating agents. Pipobroman has well-documented clinical activity against polycythemia vera and essential thrombocythemia. |
Solubility Data
| Solubility (In Vitro) |
DMSO: ~71 mg/mL (~199.4 mM) Ethanol: ~71 mg/mL |
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (5.84 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 20.8 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: ≥ 2.08 mg/mL (5.84 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 20.8 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: ≥ 2.08 mg/mL (5.84 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 20.8 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 | 2.8086 mL | 14.0430 mL | 28.0859 mL | |
| 5 mM | 0.5617 mL | 2.8086 mL | 5.6172 mL | |
| 10 mM | 0.2809 mL | 1.4043 mL | 2.8086 mL |