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Molibresib (I-BET-762) BET Inhibiteur

Name: Molibresib (I-BET-762)
Brand: Selleck Chemicals
SKU: S7189
Rating: 5 (41 reviews)

Réf. CatalogueS7189

Molibresib (I-BET-762, GSK525762, GSK525762A) est un inhibiteur des protéines BET avec une IC50 d'environ 35 nM dans un essai sans cellules. Il supprime la production de protéines pro-inflammatoires par les macrophages et bloque l'inflammation aiguë, et est très sélectif par rapport aux autres protéines contenant un bromodomaine.

Molibresib (I-BET-762) BET Inhibiteur Chemical Structure

Structure chimique

Poids moléculaire: 423.9

Aller à

Contrôle Qualité (Quality Control)

Lot : Pureté : 99.87%

99.87

Cibles apparentées	HDAC JAK Histone Methyltransferase PKC PARP HIF PRMT EZH2 AMPK Histone Acetyltransferase
Autre BET Inhibiteurs	Pelabresib (CPI-0610) ZEN-3694 (BET-IN-19) Mivebresib (ABBV-075) INCB054329 Birabresib (OTX015) I-BET151 (GSK1210151A) Apabetalone (RVX-208) AZD5153 6-hydroxy-2-naphthoic acid CPI-203 I-BRD9

Culture cellulaire, traitement et concentration de travail
(Cell Culture, Treatment & Working Concentration)

Lignées cellulaires	Type d'essai	Concentration	Temps d'incubation	Description de l'activité	PMID
HepG2	Function assay		18 hrs	Induction of human ApoA1 gene expression in stably transfected human HepG2 cells coexpressing luciferase reporter gene after 18 hrs by luminescence assay, EC50 = 0.7 μM.	21568322
HepG2	Function assay		6 hrs	Induction of human ApoA1 protein synthesis in human HepG2 cells assessed as neosynthesised radiolabeled protein secretion after 6 hrs by SDS PAGE analysis in presence of [35S]methionine	21568322
HepG2	Function assay		18 hrs	Upregulation of ApoA1 expression in human HepG2 cells assessed as concentration required to increase 70% of luciferase activity after 18 hrs by luciferase reporter gene assay, EC170 = 0.2 μM.	22386529
HepG2	Function assay		18 hrs	Induction of human ApoA1 gene expression in stably transfected human HepG2 cells coexpressing luciferase reporter gene after 18 hrs by luminescence assay, EC50 = 0.7 μM.	22924434
PBMC	Antiinflammatory assay			Antiinflammatory activity against human PBMC cells assessed as LPS-induced IL-6 production by chemiluminescence assay, IC50 = 0.31623 μM.	24015967
Raji	Function assay		4 hrs	Inhibition of BRD4 in human Raji cells assessed as reduction of MYC expression after 4 hrs, IC50 = 0.19 μM.	24900758
Rosetta2 DE3	Function assay		30 mins	Displacement of FAM-labeled ZBA248 from BRD3 BD2 (306 to 417 amino acid residues) (unknown origin) expressed in Rosetta2 DE3 cells after 30 mins by fluorescence polarization assay, Ki = 0.0303 μM.	26080064
Rosetta2 DE3	Function assay		30 mins	Displacement of FAM-labeled ZBA248 from BRD4 BD2 (333 to 460 amino acid residues) (unknown origin) expressed in Rosetta2 DE3 cells after 30 mins by fluorescence polarization assay, Ki = 0.0323 μM.	26080064
Rosetta2 DE3	Function assay		30 mins	Displacement of FAM-labeled ZBA248 from BRD4 BD1 (44 to 168 amino acid residues) (unknown origin) expressed in Rosetta2 DE3 cells after 30 mins by fluorescence polarization assay, Ki = 0.0388 μM.	26080064
Rosetta2 DE3	Function assay			Binding affinity to biotinylated BRD3 BD2 (306 to 417 amino acid residues) (unknown origin) expressed in Rosetta2 DE3 cells by bio-layer interferometry method, Kd = 0.0407 μM.	26080064
Rosetta2 DE3	Function assay			Binding affinity to biotinylated BRD2 BD2 (349 to 460 amino acid residues) (unknown origin) expressed in Rosetta2 DE3 cells by bio-layer interferometry method, Kd = 0.0454 μM.	26080064
Rosetta2 DE3	Function assay			Binding affinity to biotinylated BRD4 BD2 (333 to 460 amino acid residues) (unknown origin) expressed in Rosetta2 DE3 cells by bio-layer interferometry method, Kd = 0.0476 μM.	26080064
Rosetta2 DE3	Function assay		30 mins	Displacement of FAM-labeled ZBA248 from BRD2 BD2 (349 to 460 amino acid residues) (unknown origin) expressed in Rosetta2 DE3 cells after 30 mins by fluorescence polarization assay, Ki = 0.0492 μM.	26080064
Rosetta2 DE3	Function assay		30 mins	Displacement of FAM-labeled ZBA248 from BRD3 BD1 (24 to 144 amino acid residues) (unknown origin) expressed in Rosetta2 DE3 cells after 30 mins by fluorescence polarization assay, Ki = 0.0539 μM.	26080064
Rosetta2 DE3	Function assay		30 mins	Displacement of FAM-labeled ZBA248 from BRD2 BD1 (72 to 205 amino acid residues) (unknown origin) expressed in Rosetta2 DE3 cells after 30 mins by fluorescence polarization assay, Ki = 0.0568 μM.	26080064
Rosetta2 DE3	Function assay			Binding affinity to biotinylated BRD3 BD1 (24 to 144 amino acid residues) (unknown origin) expressed in Rosetta2 DE3 cells by bio-layer interferometry method, Kd = 0.0607 μM.	26080064
MV4-11	Cytotoxicity assay		4 days	Cytotoxicity against human MV4-11 cells harboring MLL1 fusion gene assessed as growth inhibition after 4 days by CellTiter-Glo luminescent assay, IC50 = 0.093 μM.	26080064
Rosetta2 DE3	Function assay		30 mins	Displacement of FAM-labeled ZBA248 from BRD4 BD2 (333 to 460 amino acid residues) (unknown origin) expressed in Rosetta2 DE3 cells after 30 mins by fluorescence polarization assay, IC50 = 0.0984 μM.	26080064
Rosetta2 DE3	Function assay			Binding affinity to biotinylated BRD4 BD1 (44 to 168 amino acid residues) (unknown origin) expressed in Rosetta2 DE3 cells by bio-layer interferometry method, Kd = 0.0994 μM.	26080064
Rosetta2 DE3	Function assay		30 mins	Displacement of FAM-labeled ZBA248 from BRD4 BD1 (44 to 168 amino acid residues) (unknown origin) expressed in Rosetta2 DE3 cells after 30 mins by fluorescence polarization assay, IC50 = 0.156 μM.	26080064
Rosetta2 DE3	Function assay			Binding affinity to biotinylated BRD2 BD1 (72 to 205 amino acid residues) (unknown origin) expressed in Rosetta2 DE3 cells by bio-layer interferometry method, Kd = 0.159 μM.	26080064
MOLM13	Cytotoxicity assay		4 days	Cytotoxicity against human MOLM13 cells harboring MLL1 fusion gene assessed as growth inhibition after 4 days by CellTiter-Glo luminescent assay, IC50 = 0.241 μM.	26080064
BL21(DE3)	Function assay			Binding affinity to N-terminal His6-tagged-BRD4 bromodomain 2 (unknown origin) expressed in competent Escherichia coli BL21(DE3) cells by isothermal titration calorimetry, Kd = 0.065 μM.	26367539
BL21(DE3)	Function assay			Binding affinity to N-terminal His6-tagged-BRD4 bromodomain 1 (unknown origin) expressed in competent Escherichia coli BL21(DE3) cells by isothermal titration calorimetry, Kd = 0.095 μM.	26367539
BL21(DE3)	Function assay			Binding affinity to full length N-terminal His6-tagged-BRD2 bromodomain 2 (unknown origin) expressed in competent Escherichia coli BL21(DE3) cells by isothermal titration calorimetry, Kd = 0.1 μM.	26367539
BL21(DE3)	Function assay			Binding affinity to full length N-terminal His6-tagged-BRD2 bromodomain 1 (unknown origin) expressed in competent Escherichia coli BL21(DE3) cells by isothermal titration calorimetry, Kd = 0.23 μM.	26367539
BL21(DE3)-R3-pRARE2	Function assay			Inhibition of human His-tagged BRD4 bromodomain 2 expressed in Escherichia coli BL21(DE3)-R3-pRARE2 cells by FRET assay, IC50 = 0.036 μM.	26731490
BL21(DE3)-R3-pRARE2	Function assay			Inhibition of human His-tagged BRD4 bromodomain 1 expressed in Escherichia coli BL21(DE3)-R3-pRARE2 cells by FRET assay, IC50 = 0.036 μM.	26731490
Rosetta2 DE3	Function assay		30 mins	Inhibition of FAM-labeled ZBA248 binding to recombinant human N-terminal His6-tagged BRD4 bromodomain 2 (333 to 460 residues) expressed in Rosetta2 DE3 cells after 30 mins by Flourescence polarization assay, Ki = 0.023 μM.	28463487
Rosetta2 DE3	Function assay		30 mins	Inhibition of FAM-labeled ZBA248 binding to recombinant human N-terminal His6-tagged BRD4 bromodomain 1 (44 to 168 residues) expressed in Rosetta2 DE3 cells after 30 mins by Flourescence polarization assay, Ki = 0.0464 μM.	28463487
Rosetta2 DE3	Function assay		30 mins	Inhibition of FAM-labeled ZBA248 binding to recombinant human N-terminal His6-tagged BRD4 bromodomain 2 (333 to 460 residues) expressed in Rosetta2 DE3 cells after 30 mins by Flourescence polarization assay, IC50 = 0.0775 μM.	28463487
MV4-11	Growth inhibition assay		4 days	Growth inhibition of human MV4-11 cells after 4 days by WST-8 assay, IC50 = 0.093 μM.	28463487
Rosetta2 DE3	Function assay		30 mins	Inhibition of FAM-labeled ZBA248 binding to recombinant human N-terminal His6-tagged BRD4 bromodomain 1 (44 to 168 residues) expressed in Rosetta2 DE3 cells after 30 mins by Flourescence polarization assay, IC50 = 0.145 μM.	28463487
MOLM13	Growth inhibition assay		4 days	Growth inhibition of human MOLM13 cells after 4 days by WST-8 assay, IC50 = 0.241 μM.	28463487
TY82	Antiproliferative assay		72 hrs	Antiproliferative activity against human TY82 cells after 72 hrs by CCK8 assay, IC50 = 0.2 μM.	28586718
MM1S	Antiproliferative assay		72 hrs	Antiproliferative activity against human MM1S cells after 72 hrs by CCK8 assay, IC50 = 0.23 μM.	28586718
BL21 (DE3)-codon plus-RIL	Function assay		4 hrs	Inhibition of JQ1-FITC binding to His6-tagged BRD4-BD1 (unknown origin) expressed in Escherichia coli BL21 (DE3)-codon plus-RIL cells incubated in dark for 4 hrs by fluorescence anisotropy assay, IC50 = 0.26 μM.	28586718
THP1	Antiproliferative assay			Antiproliferative activity against human THP1 cells, IC50 = 0.29 μM.	28939121
TY82	Antiproliferative assay			Antiproliferative activity against human TY82 cells, IC50 = 0.39 μM.	28939121
NALM16	Cytotoxicity assay		5 days	Cytotoxicity against human NALM16 cells assessed as reduction in cell viability after 5 days by CellTiter-Glo assay, EC50 = 0.27 μM.	29170024
NALM6	Cytotoxicity assay		5 days	Cytotoxicity against human NALM6 cells assessed as reduction in cell viability after 5 days by CellTiter-Glo assay, EC50 = 0.39 μM.	29170024
697	Cytotoxicity assay		5 days	Cytotoxicity against human 697 cells assessed as reduction in cell viability after 5 days by CellTiter-Glo assay, EC50 = 1.17 μM.	29170024
HD-MB03	Cytotoxicity assay		5 days	Cytotoxicity against human HD-MB03 cells assessed as reduction in cell viability after 5 days by CellTiter-Glo assay, EC50 = 3.5 μM.	29170024
A673	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for A673 cells	29435139
DAOY	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for DAOY cells	29435139
Saos-2	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Saos-2 cells	29435139
BT-37	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for BT-37 cells	29435139
RD	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for RD cells	29435139
MG 63 (6-TG R)	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for MG 63 (6-TG R) cells	29435139
NB1643	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB1643 cells	29435139
OHS-50	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for OHS-50 cells	29435139
Rh41	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh41 cells	29435139
SJ-GBM2	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SJ-GBM2 cells	29435139
SK-N-MC	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SK-N-MC cells	29435139
NB-EBc1	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB-EBc1 cells	29435139
LAN-5	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for LAN-5 cells	29435139
TY82	Antiproliferative assay		72 hrs	Antiproliferative activity against human TY82 cells after 72 hrs by CCK8 assay, IC50 = 0.3043 μM.	29525435
MM1S	Antiproliferative assay		72 hrs	Antiproliferative activity against human MM1S cells after 72 hrs by CCK8 assay, IC50 = 0.3492 μM.	29525435
TY82	Function assay	0.2 to 1 uM	24 hrs	Inhibition of BRD4 in human TY82 cells assessed as reduction in c-Myc protein expression at 0.2 to 1 uM after 24 hrs by Western blot analysis	29525435
TY82	Function assay	0.2 to 1 uM	24 hrs	Inhibition of BRD4 in human TY82 cells assessed as reduction in c-Myc mRNA expression at 0.2 to 1 uM after 24 hrs by RT-PCR analysis	29525435
TY82 or NCI-H1299	Function assay	0.2 to 1 uM	24 hrs	Inhibition of BRD4 in human TY82 or NCI-H1299 cells assessed as reduction in PD-L1 protein expression at 0.2 to 1 uM after 24 hrs by Western blot analysis	29525435
TY82 or NCI-H1299	Function assay	0.2 to 1 uM	24 hrs	Inhibition of BRD4 in human TY82 or NCI-H1299 cells assessed as reduction in PD-L1 mRNA expression at 0.2 to 1 uM after 24 hrs by RT-PCR analysis	29525435
C4-2B	Antiproliferative assay		96 hrs	Antiproliferative activity against human C4-2B cells after 96 hrs by Cell-Titer glo reagent based luminescence assay	29541371
22Rv1	Antiproliferative assay		96 hrs	Antiproliferative activity against human 22Rv1 cells after 96 hrs by Cell-Titer glo reagent based luminescence assay	29541371
LNCAP	Antiproliferative assay		96 hrs	Antiproliferative activity against human LNCAP cells after 96 hrs by Cell-Titer glo reagent based luminescence assay	29541371
HL60	Cytotoxicity assay			Cytotoxicity against human HL60 cells by MTS assay, IC50 = 0.12 μM.	29657099
Raji	Function assay			Inhibition of BRD4-BD1 in human Raji cells assessed as downregulation of MYC gene expression by PCR method, IC50 = 0.132 μM.	29657099
LNCAP	Antiproliferative assay			Antiproliferative activity against human LNCAP cells, IC50 = 0.3565 μM.	29758518
MV411	Cytotoxicity assay		72 hrs	Cytotoxicity against human MV411 cells after 72 hrs by CellTiter-Glo assay, IC50 = 0.8 μM.	30268702
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Informations chimiques, stockage et stabilité (Chemical Information, Storage & Stability)

Poids moléculaire	423.9	Formule	C₂₂H₂₂ClN₅O₂	Stockage (À compter de la date de réception)	3 ans-20°Cpoudre
N° CAS	1260907-17-2	Télécharger le SDF		Stockage des solutions mères	1 an-80°Cen solvant 1 mois-20°Cen solvant
Synonymes	GSK525762, GSK525762A			Smiles	CCNC(=O)CC1C2=NN=C(N2C3=C(C=C(C=C3)OC)C(=N1)C4=CC=C(C=C4)Cl)C

Solubilité (Solubility)

In vitro
Lot:

DMSO : 84 mg/mL (198.15 mM)
(Le DMSO contaminé par l'humidité peut réduire la solubilité. Utiliser du DMSO frais et anhydre.)

Ethanol : 42 mg/mL

Water : Insoluble

Calculateur de molarité

Masse	Concentration	Volume	Poids moléculaire
=	×	×

Calculateur de dilution Calculateur de poids moléculaire

In vivo Lot:
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Clear solution	5%DMSO 1 40%PEG300 2 5%Tween80 3 50%ddH2O Validé par les laboratoires Selleck. Si vous avez besoin d'ajustements à cette formulation, contactez notre équipe commerciale pour des tests personnalisés.	4.250mg/ml (10.03mM)	Taking the 1 mL working solution as an example, add 50 μL of 85 mg/ml clarified DMSO stock solution to 400 μL of PEG300, mix evenly to clarify it; add 50 μL of Tween80 to the above system, mix evenly to clarify; then continue to add 500 μL of ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.

Calculateur de formulation in vivo (Solution claire)

Étape 1 : Saisir les informations ci-dessous (Recommandé : Un animal supplémentaire pour tenir compte des pertes pendant l'expérience)

Dosage : mg/kg Poids moyen des animaux : g Volume de dosage par animal :μL Nombre d'animaux :

Étape 2 : Saisir la formulation in vivo (Ceci est seulement le calculateur, pas la formulation. Veuillez nous contacter d'abord s'il n'y a pas de formulation in vivo dans la section Solubilité.)

% DMSO + % + % Tween 80 + % ddH₂O

%DMSO+ %

Résultats du calcul :

Concentration de travail : mg/ml;

Méthode de préparation du liquide maître DMSO : mg médicament prédissous dans μL DMSO ( Concentration du liquide maître mg/mL, Veuillez nous contacter d'abord si la concentration dépasse la solubilité du DMSO du lot de médicament. )

Méthode de préparation de la formulation in vivo : Prendre μL DMSO liquide maître, puis ajouterμL PEG300, mélanger et clarifier, puis ajouterμL Tween 80, mélanger et clarifier, puis ajouter μL ddH₂O, mélanger et clarifier.

Méthode de préparation de la formulation in vivo : Prendre μL DMSO liquide maître, puis ajouter μL Huile de maïs, mélanger et clarifier.

Note : 1. Veuillez vous assurer que le liquide est clair avant d'ajouter le solvant suivant.
2. Assurez-vous d'ajouter le(s) solvant(s) dans l'ordre. Vous devez vous assurer que la solution obtenue, lors de l'ajout précédent, est une solution claire avant de procéder à l'ajout du solvant suivant. Des méthodes physiques telles que le vortex, les ultrasons ou le bain-marie chaud peuvent être utilisées pour faciliter la dissolution.

Mécanisme d'action (Mechanism of Action)

Targets/IC₅₀/Ki	BET proteins (Cell-free assay) 35 nM
In vitro	Molibresib (I-BET-762) est un inhibiteur des protéines BET (bromodomain and extra terminal domain), BRD2, BRD3 et BRD4, qui se lie aux bromodomaines en tandem de BET avec un K_d de 50,5–61,3 nM et déplace un peptide H4 tétra-acétylé pré-lié aux bromodomaines en tandem de BET avec une IC50 de 32,5–42,5 nM en analyse FRET. Ce composé occupe la poche de liaison de l'acétyl-lysine des protéines BET et inhibe leur liaison aux histones acétylées, perturbant ainsi la formation de complexes de chromatine essentiels à l'expression des gènes inflammatoires. Le traitement avec celui-ci pendant les 2 premiers jours de différenciation modifie la production de cytokines par les cellules T CD4⁺, augmentant l'expression de plusieurs produits géniques anti-inflammatoires et diminuant l'expression de plusieurs cytokines pro-inflammatoires.
Essai kinase	Titrations par transfert d'énergie de résonance par fluorescence (FRET)
Essai kinase	Titrations par transfert d'énergie de résonance par fluorescence (FRET). Molibresib (I-BET-762) est titré contre BRD2 (200 nM), BRD3 (100 nM) et BRD4 (50 nM) dans 50 mM HEPES pH 7,5, 50 mM NaCl, 0,5 mM CHAPS en présence de peptide d'histone H4 tétra-acétylé (200 nM). Après équilibration pendant 1 heure, l'interaction protéine bromodomaine : peptide est détectée par FRET après l'ajout de 2 nM de streptavidine marquée au cryptate d'europium et de 10 nM d'anticorps anti-6His marqué au XL-665 dans un tampon d'essai contenant 0,05 % (v/v) de BSA et 400 mM de KF. Les plaques sont lues à l'aide d'un lecteur de plaques Envision (excitation 320 nm, émission 615 nm et 665 nm).
In vivo	Molibresib (I-BET-762) confère une protection contre le choc endotoxique induit par le lipopolysaccharide et la septicémie induite par les bactéries. Une dose unique de ce composé appliquée 1,5 h après l'injection de LPS guérit les souris, et des injections deux fois par jour pendant 2 jours les protègent contre la mort causée par la septicémie. Un traitement limité avec celui-ci exclusivement pendant l'amorçage précoce a inhibé la capacité des cellules T 2D2 différenciées Th1 à induire une neuroinflammation dans un modèle murin d'encéphalomyélite auto-immune expérimentale (EAE).
Références	[1] https://pubmed.ncbi.nlm.nih.gov/21068722/ [2] https://pubmed.ncbi.nlm.nih.gov/22912406/

Applications (Applications)

Méthodes	Biomarqueurs	Images	PMID
Growth inhibition assay	Cell viability		26840085

Informations sur l'essai clinique (Clinical Trial Information)

(données du https://clinicaltrials.gov, mis à jour le 2024-05-22)

Numéro NCT	Recrutement	Conditions	Promoteur/Collaborateurs	Date de début	Phases
NCT03266159	Withdrawn	Solid Tumours	GlaxoSmithKline	November 27 2017	Phase 2
NCT02964507	Terminated	Neoplasms	GlaxoSmithKline	February 2 2017	Phase 1
NCT01943851	Completed	Neoplasms	GlaxoSmithKline	May 14 2014	Phase 2
NCT01587703	Completed	Carcinoma Midline	GlaxoSmithKline	March 28 2012	Phase 1

C1=C0/X	C1:	LOG(C1):
C2=C1/X	C2:	LOG(C2):
C3=C2/X	C3:	LOG(C3):
C4=C3/X	C4:	LOG(C4):
C5=C4/X	C5:	LOG(C5):
C6=C5/X	C6:	LOG(C6):
C7=C6/X	C7:	LOG(C7):
C8=C7/X	C8:	LOG(C8):