COLESTIPOL HYDROCHLORIDE

First approved in 1977

Description
Sources: http://www.google.com/patents/WO1993000915A1?cl=enhttp://www.huntsman.com/performance_products/Media%20Library/a_MC348531CFA3EA9A2E040EBCD2B6B7B06/Products_MC348531D0B9FA9A2E040EBCD2B6B7B06/Amines_MC348531D0BECA9A2E040EBCD2B6B7B06/Ethyleneamines_MC348531D0CD3A9A2E040EBCD2B6B7B06/files/tetraethylenepentamine_tepa.pdf
Curator's Comment: Description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/26581493 | http://pubs.acs.org/doi/abs/10.1021/ic50099a028?journalCode=inocaj | http://pubs.acs.org/doi/abs/10.1021/ic50048a017?journalCode=inocaj | https://clinicaltrials.gov/ct2/show/NCT01484470 | https://www.ncbi.nlm.nih.gov/pubmed/18209724 | https://www.ncbi.nlm.nih.gov/pubmed/16219531

Tetraethylenepentamine (TEPA) is a low-molecular-weight linear polyamine exerting metal-chelating properties. TEPA is widely used in industrial applications. The principal hazards that arise in working with TEPA are those associated with similar organic amines; namely, a corrosive action on skin and eyes. TEPA biological activity was attributed to its effect on cellular Cu levels as (a) treatment with TEPA resulted in reduction of cellular Cu, and (b) excess of Cu reversed TEPA's activity and accelerated differentiation. TEPA was shown to attenuate the differentiation of ex vivo cultured hematopoietic cells resulting in preferential expansion of early progenitors. A phase I/II trial was performed to test the feasibility and safety of transplantation of CD133+ cord blood (CB) hematopoietic progenitors cultured in media containing stem cell factor, FLT-3 ligand, interleukin-6, thrombopoietin and TEPA. Transplanting a population of CD133+ CB cells which were expanded ex vivo for 21 days using SCF, FLT3, IL-6, TPO and the copper chelator TEPA (StemEx) was feasible. The expanded cells were well tolerated, with no infusion-related adverse events observed.

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Oxidative Stress 160 Target ID: WP408 Sources: https://www.ncbi.nlm.nih.gov/pubmed/18047399	Inhibitor 8297
Copper 16 Target ID: CHEMBL2363057 Sources: http://pubs.acs.org/doi/abs/10.1021/ic50099a028?journalCode=inocaj	Chelating Agent 142
Bile acids 3 Target ID: CHEMBL2364175 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2014/017563s023,020222s005lbl.pdf	Binding Agent 1064

Conditions

Condition	Modality	Targets	Highest Phase	Product
Hematologic malignancies 19 Sources: https://www.ncbi.nlm.nih.gov/pubmed/18209724 http://www.bloodjournal.org/content/122/21/295?sso-checked=true https://clinicaltrials.gov/ct2/show/NCT01484470	Primary		Phase II 1132	StemEx Approved Use Unknown
Primary hypercholesterolemia 3 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2014/017563s023,020222s005lbl.pdf	Palliative		Approved 8429	COLESTID Approved Use COLESTID Granules and FLAVORED COLESTID Granules are indicated as adjunctive therapy to diet for the reduction of elevated serum total and low-density lipoprotein (LDL) cholesterol in patients with primary hypercholesterolemia (elevated low density lipoproteins [LDL] cholesterol) who do not respond adequately to diet. Generally, COLESTID and FLAVORED COLESTID have no clinically significant effect on serum triglycerides, but with its use triglyceride levels may be raised in some patients. Launch Date 1977

PubMed

Title	Date	PubMed
Treatment of heterozygous familial hypercholesterolemia with lipid-lowering drugs.	1989 Jan-Feb	2492189
Inhibitors of hydroxymethylglutaryl coenzyme A reductase for treating hypercholesterolaemia.	1990 Sep 29	2224231
Currently available hypolipidaemic drugs and future therapeutic developments.	1995 Oct	8593127
Effects of prolonged intensive lipid-lowering therapy on the characteristics of carotid atherosclerotic plaques in vivo by MRI: a case-control study.	2001 Oct	11597936
Purification, bacteriolytic activity, and specificity of beta-lytic protease from Lysobacter sp. IB-9374.	2003	16233362
Pre-clinical development of cord blood-derived progenitor cell graft expanded ex vivo with cytokines and the polyamine copper chelator tetraethylenepentamine.	2004	16146887
Controlled three-dimensional immobilization of biomolecules on chemically patterned surfaces.	2004 Aug 26	15288945
Linear polyamine copper chelator tetraethylenepentamine augments long-term ex vivo expansion of cord blood-derived CD34+ cells and increases their engraftment potential in NOD/SCID mice.	2004 Jun	15183895
New poly(d-glucaramidoamine)s induce DNA nanoparticle formation and efficient gene delivery into mammalian cells.	2004 Jun 23	15198572
Pharmaceutical care for elderly patients shared between community pharmacists and general practitioners: a randomised evaluation. RESPECT (Randomised Evaluation of Shared Prescribing for Elderly people in the Community over Time) [ISRCTN16932128].	2004 Jun 7	15182379
Mevinolin and colestipol stimulate receptor-mediated clearance of low density lipoprotein from plasma in familial hypercholeserolemia heterozygotes. 1983.	2004 Oct	15531277
Effectiveness and tolerability of ezetimibe add-on therapy to a bile acid resin-based regimen for hypercholesterolemia.	2004 Sep 15	15374793
Effect of time of administration on cholesterol-lowering by psyllium: a randomized cross-over study in normocholesterolemic or slightly hypercholesterolemic subjects.	2004 Sep 28	15453909
NGF promotes copper accumulation required for optimum neurite outgrowth and protein methylation.	2005 Apr	15627265
Sodium monofluoroacetate (Compound 1080) poisoning in dogs.	2005 Aug	16119418
Liver X receptor alpha interferes with SREBP1c-mediated Abcd2 expression. Novel cross-talk in gene regulation.	2005 Dec 16	16249184
A highly efficient preparative-scale generic immunoaffinity chromatography method for the purification of antibodies to hydrophobic haptens: purification procedure and monitoring tests.	2005 Dec 5	16202669
Large scale synthesis of tellurium nanoribbons in tetraethylene pentamine aqueous solution and the stability of tellurium nanoribbons in ethanol and water.	2005 Dec 8	16853963
Complementary care. How statin alternatives stack up. Some help control cholesterol; others are potentially harmful.	2005 Jan	15795954
A bitter tale.	2005 Jan 6	15635787
Mitochondrial membrane potential is reduced in copper-deficient C2C12 cells in the absence of apoptosis.	2005 Jul	16037610
Hydroxyl stereochemistry and amine number within poly(glycoamidoamine)s affect intracellular DNA delivery.	2005 Mar 9	15740138
[Charge control and IR analysis of amine on diarylide yellow pigment PY14].	2005 Oct	16395888
Chelatable cellular copper modulates differentiation and self-renewal of cord blood-derived hematopoietic progenitor cells.	2005 Oct	16219531
Low-density lipoprotein-lowering medication and platelet function.	2006	16877882
Genetically determined apo B levels and peak LDL density predict angiographic response to intensive lipid-lowering therapy.	2006 Apr	16594908
Sequestration of biogenic amines by alginic and fulvic acids.	2006 Aug 1	16690202
Capillary zone electrophoresis method for the determination of inorganic anions and formic acid in honey.	2006 Dec 13	17147409
Profiling preparations of recombinant birch pollen allergen Bet v 1a with capillary zone electrophoresis in pentamine modified fused-silica capillaries.	2006 Jul 24	16504605
Clinical utility of bile acid sequestrants in the treatment of dyslipidemia: a scientific review.	2006 Mar	16553100
Prediction of estrogen receptor agonists and characterization of associated molecular descriptors by statistical learning methods.	2006 Nov	16497524
Synthesis of a quaternary amine anion exchange resin and study [of] its adsorption behaviour for chromate oxyanions.	2006 Sep 21	16682117
Atherogenic dyslipidemia in metabolic syndrome and type 2 diabetes: therapeutic options beyond statins.	2006 Sep 26	17002798
Regression or reduction in progression of atherosclerosis, and avoidance of coronary events, with lovastatin in patients with or at high risk of cardiovascular disease: a review.	2007	17705568
One-dimensional indium sulfides with transition metal complexes of polyamines.	2007 Aug 6	17622136
Therapeutic approach to FSGS in children.	2007 Jan	17109140
The use of colesevelam hydrochloride in the treatment of dyslipidemia: a review.	2007 Oct	17931091
Telmisartan/hydrochlorothiazide versus valsartan/hydrochlorothiazide in obese hypertensive patients with type 2 diabetes: the SMOOTH study.	2007 Oct 2	17910747
Fish-oil esters of plant sterols differ from vegetable-oil sterol esters in triglycerides lowering, carotenoid bioavailability and impact on plasminogen activator inhibitor-1 (PAI-1) concentrations in hypercholesterolemic subjects.	2007 Oct 25	17961204
In situ ligand reactions under hydrothermal conditions afford a novel zinc-substituted polyoxovanadate dimer.	2007 Oct 29	17915859
Tetraethylenepentamine-directed controllable synthesis of wurtzite ZnSe nanostructures with tunable morphology.	2008	18792043
Bile acid sequestrants as a therapeutic option for glucose lowering in type 2 diabetes mellitus.	2008 Jul-Aug	18753111
Absorption spectroscopic and FTIR studies on EDA complexes between TNT (2,4,6-trinitrotoluene) with amines in DMSO and determination of the vertical electron affinity of TNT.	2008 Jun	17765603
Plasma PCSK9 levels are significantly modified by statins and fibrates in humans.	2008 Jun 11	18547436
Synthesis of magnetic chelating resins functionalized with tetraethylenepentamine for adsorption of molybdate anions from aqueous solutions.	2008 Jun 30	18177999
Preparation of polyurea capsules using electrocapillary emulsification.	2008 Oct 15	18768303
A capillary electrophoretic method for fingerprinting low molecular weight heparins.	2008 Sep 15	18572011
Management of complex lipid abnormalities with a fixed dose combination of simvastatin and extended release niacin.	2009	19436666
Does nicotinic acid (niacin) lower blood pressure?	2009 Jan	19054161
Primary biliary cirrhosis.	2009 Sep	19603170

Patents

Sample Use Guides

In Vivo Use Guide

The recommended daily adult dose is 5-30 g (granules) or 2-16 g (tablets) given once or in divided doses.

Route of Administration: Oral

In Vitro Use Guide

In vitro binding capacity is 1 mequiv cholic acid/g.

Name

Type

Language

COLESTIPOL HYDROCHLORIDE

Official Name

English

COLESTIPOL HYDROCHLORIDE [ORANGE BOOK]

Common Name

English

COLESTIPOL HYDROCHLORIDE [USAN]

Common Name

English

COLESTIPOL HYDROCHLORIDE [VANDF]

Common Name

English

COLESTIPOL HCL

Common Name

English

COLESTIPOL HYDROCHLORIDE [MART.]

Common Name

English

Colestipol hydrochloride [WHO-DD]

Common Name

English

COLESTIPOL HYDROCHLORIDE [USP-RS]

Common Name

English

COLESTIPOL HYDROCHLORIDE [USP MONOGRAPH]

Common Name

English

COLESTID

Brand Name

English

COLESTIPOL HYDROCHLORIDE [MI]

Common Name

English

Copolymer of diethylenetriamine and 1-chloro-2,3-epoxypropane, hydrochloride (with approximately 1 out of 5 amine nitrogens protonated)

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C98148