solo per uso di ricerca

Ganetespib (STA-9090) HSP90 Inhibitor

Name: Ganetespib (STA-9090)
Brand: Selleck Chemicals
SKU: S1159
Rating: 5 (80 reviews)

N. Cat.: S1159

Ganetespib (STA-9090) è un inibitore di HSP90 con IC50 di 4 nM nelle cellule OSA 8, induce l'apoptosi delle cellule OSA mentre gli osteoblasti normali non sono influenzati; metabolita attivo di STA-1474. Fase 3.

Ganetespib (STA-9090) HSP Inibitore Chemical Structure

Struttura chimica

Peso molecolare: 364.4

Vai a

Controllo Qualità (Quality Control)

Lotto: Purezza: 99.97%

99.97

Target correlati	Akt Wnt/beta-catenin PKC ROCK Microtubule Associated Integrin Bcr-Abl Actin FAK Kinesin
Altro HSP Inibitori	Tanespimycin (17-AAG) Elesclomol (STA-4783) Luminespib (NVP-AUY922) Alvespimycin (17-DMAG) Hydrochloride VER-155008 Onalespib (AT13387) BIIB021 Celastrol (Tripterine) Zelavespib (PU-H71) NVP-BEP800

Coltura cellulare, trattamento e concentrazione di lavoro
(Cell Culture, Treatment & Working Concentration)

Linee cellulari	Tipo di saggio	Concentrazione	Tempo di incubazione	Formulazione	Descrizione dell'attività	PMID
NCI-H1975	Growth Inhibition Assay		72 h		IC50=8 nM	22144665
NCI-H1975	Growth Inhibition Assay		48 h		IC50=16 nM	22144665
Calu-6	Growth Inhibition Assay				IC50=64 nM	23012248
Calu-1	Growth Inhibition Assay				IC50=58 nM	23012248
H2122	Growth Inhibition Assay				IC50=53 nM	23012248
A549	Growth Inhibition Assay				IC50=43 nM	23012248
H358	Growth Inhibition Assay				IC50=29 nM	23012248
H1734	Growth Inhibition Assay				IC50=28 nM	23012248
H727	Growth Inhibition Assay				IC50=28 nM	23012248
COR-L23	Growth Inhibition Assay				IC50=22 nM	23012248
H1792	Growth Inhibition Assay				IC50=20 nM	23012248
H2009	Growth Inhibition Assay				IC50=19 nM	23012248
SK-LU-1	Growth Inhibition Assay				IC50=18 nM	23012248
H2212	Growth Inhibition Assay				IC50=17 nM	23012248
H441	Growth Inhibition Assay				IC50=14 nM	23012248
H2030	Growth Inhibition Assay				IC50=12 nM	23012248
H23	Growth Inhibition Assay				IC50=11 nM	23012248
HOP-62	Growth Inhibition Assay				IC50=11 nM	23012248
IA-LM	Growth Inhibition Assay				IC50=10 nM	23012248
H460	Growth Inhibition Assay				IC50=8 nM	23012248
H157	Growth Inhibition Assay				IC50=7 nM	23012248
H1355	Growth Inhibition Assay				IC50=5 nM	23012248
VCaP	Growth Inhibition Assay				IC50=7 nM	23152004
LNCaP	Growth Inhibition Assay				IC50=8 nM	23152004
Ramos-RA1	Growth Inhibition Assay				IC50=7.4 nM	23303741
Karpas-299	Growth Inhibition Assay				IC50=9.6 nM	23303741
Kasumi-1	Growth Inhibition Assay				IC50=5.8 nM	23303741
CCRF-CEM (2)	Growth Inhibition Assay				IC50=7.2 nM	23303741
CCRF-CEM (1)	Growth Inhibition Assay				IC50=12.5 nM	23303741
MOLT-4	Growth Inhibition Assay				IC50=10.6 nM	23303741
RS4;11	Growth Inhibition Assay				IC50=13.5 nM	23303741
COG-LL-317	Growth Inhibition Assay				IC50=4.4 nM	23303741
NALM-6	Growth Inhibition Assay				IC50=11.7 nM	23303741
CHLA-136	Growth Inhibition Assay				IC50=23.2 nM	23303741
CHLA-90	Growth Inhibition Assay				IC50=22.3 nM	23303741
NB-EBc1	Growth Inhibition Assay				IC50=16.8 nM	23303741
NB-1643	Growth Inhibition Assay				IC50=7.4 nM	23303741
SJ-GBM2	Growth Inhibition Assay				IC50=12.9 nM	23303741
CHLA-258	Growth Inhibition Assay				IC50=6.4 nM	23303741
CHLA-10	Growth Inhibition Assay				IC50=5.7 nM	23303741
CHLA-9	Growth Inhibition Assay				IC50=4.6 nM	23303741
TC-71	Growth Inhibition Assay				IC50=4.5 nM	23303741
CHLA-266	Growth Inhibition Assay				IC50=27.1 nM	23303741
BT-12	Growth Inhibition Assay				IC50=14.3 nM	23303741
Rh30	Growth Inhibition Assay				IC50=5.6 nM	23303741
Rh18	Growth Inhibition Assay				IC50=6.2 nM	23303741
Rh41	Growth Inhibition Assay				IC50=10.4 nM	23303741
RD	Growth Inhibition Assay				IC50=8 nM	23303741
K033	Apoptosis Assay	100 nM	72 h		significantly induces apoptosis	23418523
M23	Apoptosis Assay	100 nM	72 h		significantly induces apoptosis	23418523
K029	Apoptosis Assay	100 nM	72 h		significantly induces apoptosis	23418523
K028	Apoptosis Assay	100 nM	72 h		significantly induces apoptosis	23418523
K008	Apoptosis Assay	100 nM	72 h		significantly induces apoptosis	23418523
K033	Function Assay	250 nM	24 h		induces a modest increase in G1 population	23418523
M23	Function Assay	250 nM	24 h		induces G1 and G2/M arrest	23418523
K029	Function Assay	250 nM	24 h		induces G1 arrest	23418523
K028	Function Assay	250 nM	24 h		induces G2 arrest	23418523
K008	Function Assay	250 nM	24 h		induces G2 arrest	23418523
K033	Cell Viability Assay				IC50=75.5 nM	23418523
M23	Cell Viability Assay				IC50=37.5 nM	23418523
K029	Cell Viability Assay				IC50=46 nM	23418523
K028	Cell Viability Assay				IC50=84 nM	23418523
K008	Cell Viability Assay				IC50=60 nM	23418523
H3122	Cell Viability Assay	0-1000 nM	72 h		IC50=10 nM	23533265
H2228	Cell Viability Assay	0-1000 nM	72 h		IC50=13 nM	23533265
A1847	Apoptosis Assay	10-100 nM	24/48/72 h		induces apoptosis time and dose dependently	23900136
OVCAR-8	Apoptosis Assay	10-100 nM	24/48/72 h		induces apoptosis time and dose dependently	23900136
OVCAR-5	Apoptosis Assay	10-100 nM	24/48/72 h		induces apoptosis time and dose dependently	23900136
SKOV-3	Cell Viability Assay	0-1000 nM	72 h		inhibits cell viability dose dependently	23900136
A1847	Cell Viability Assay	0-1000 nM	72 h		inhibits cell viability dose dependently	23900136
OVCAR-8	Cell Viability Assay	0-1000 nM	72 h		inhibits cell viability dose dependently	23900136
OVCAR-5	Cell Viability Assay	0-1000 nM	72 h		inhibits cell viability dose dependently	23900136
H146	Function Assay	30 nM	72 h		induces persistent G2/M phase arrest	24166505
GLC4	Function Assay	30 nM	72 h		induces persistent G2/M phase arrest	24166505
H82	Function Assay	30 nM	72 h		induces persistent G2/M phase arrest	24166505
AC3	Growth Inhibition Assay				IC50=25.9 nM	24166505
H1173	Growth Inhibition Assay				IC50=12.62 nM	24166505
H792	Growth Inhibition Assay				IC50=45.07 nM	24166505
H620	Growth Inhibition Assay				IC50=32.67 nM	24166505
N592	Growth Inhibition Assay				IC50=14.12 nM	24166505
H526	Growth Inhibition Assay				IC50=21.64 nM	24166505
H187	Growth Inhibition Assay				IC50=24.99 nM	24166505
H146	Growth Inhibition Assay				IC50=28.51 nM	24166505
H128	Growth Inhibition Assay				IC50=69.55 nM	24166505
H69	Growth Inhibition Assay				IC50=83.36 nM	24166505
GLC4	Growth Inhibition Assay				IC50=20.47 nM	24166505
H82	Growth Inhibition Assay				IC50=30.27 nM	24166505
MDA-MB-231	Function Assay	100 nM	24 h		inhibits the migratory and invasive capacity	24173541
BT-20	Function Assay	100/250 nM	24 h		resulted in a dose-dependent destabilization of EGFR, IGF-IR, MET, and CRAF	24173541
MDA-MB-435	Function Assay	100 nM	30 min		inhibits accumulation of HIF-1α	24248265
MDA-MB-231	Function Assay	100 nM	30 min		inhibits accumulation of HIF-1α	24248265
HCC2998	Growth Inhibition Assay				IC50=128 nM	24682747
SK-CO-1	Growth Inhibition Assay				IC50=81 nM	24682747
LS-123	Growth Inhibition Assay				IC50=73 nM	24682747
SNU-C2B	Growth Inhibition Assay				IC50=45 nM	24682747
LS-1034	Growth Inhibition Assay				IC50=31 nM	24682747
LoVo	Growth Inhibition Assay				IC50=22 nM	24682747
COLO-678	Growth Inhibition Assay				IC50=21 nM	24682747
NCI-H747	Growth Inhibition Assay				IC50=17 nM	24682747
COLO-205	Growth Inhibition Assay				IC50=14 nM	24682747
HCT 116	Growth Inhibition Assay				IC50=14 nM	24682747
HuTu-80	Growth Inhibition Assay				IC50=13 nM	24682747
HCT-15	Growth Inhibition Assay				IC50=8 nM	24682747
SW620	Growth Inhibition Assay				IC50=8 nM	24682747
LS-411 N	Growth Inhibition Assay				IC50=5 nM	24682747
RKO	Growth Inhibition Assay				IC50=4 nM	24682747
SW780	Growth Inhibition Assay				IC50=3451 nM	24784839
RT4	Growth Inhibition Assay				IC50=1733 nM	24784839
TCCSUP	Growth Inhibition Assay				IC50=142 nM	24784839
MGH-U3	Growth Inhibition Assay				IC50=53 nM	24784839
HT-1197	Growth Inhibition Assay				IC50=53 nM	24784839
5637	Growth Inhibition Assay				IC50=44 nM	24784839
35612	Growth Inhibition Assay				IC50=38 nM	24784839
KU-19-19	Growth Inhibition Assay				IC50=36 nM	24784839
LB831-BLC	Growth Inhibition Assay				IC50=34 nM	24784839
UM-UC3	Growth Inhibition Assay				IC50=33 nM	24784839
647-V	Growth Inhibition Assay				IC50=27 nM	24784839
HT-1376	Growth Inhibition Assay				IC50=21 nM	24784839
J82	Growth Inhibition Assay				IC50=18 nM	24784839
BFTC	Growth Inhibition Assay				IC50=17 nM	24784839
SCaBER	Growth Inhibition Assay				IC50=10 nM	24784839
639-V	Growth Inhibition Assay				IC50=10 nM	24784839
RT112	Growth Inhibition Assay				IC50=9 nM	24784839
T24	Growth Inhibition Assay				IC50=7 nM	24784839
SW-1710	Growth Inhibition Assay				IC50=6 nM	24784839
DSH1	Growth Inhibition Assay				IC50=6 nM	24784839
CAL27	Cytoxicity Assay	10/50 nM	24 h		decreases cell proliferation dose dependently	25205430
Detroit562	Cytoxicity Assay	10/50 nM	24 h		decreases cell proliferation dose dependently	25205430
FUDA	Cytoxicity Assay	10/50 nM	24 h		decreases cell proliferation dose dependently	25205430
SCC25	Cytoxicity Assay	10/50 nM	24 h		decreases cell proliferation dose dependently	25205430
HT-29	Function Assay	50nM	24 h	DMSO	induced G0/G1 arrest	25210794
HCT-116	Function Assay	50nM	24 h	DMSO	induced G0/G1 arrest	25210794
MGC-803	Function Assay	0.1-1000 nM	24 h		induces G2/M cell-cycle arrest	25590805
MKN-28	Cell Viability Assay	0.1-1000 nM	72 h		inhibits cell viability dose dependently	25590805
SGC-7901	Cell Viability Assay	0.1-1000 nM	72 h		inhibits cell viability dose dependently	25590805
MGC-803	Cell Viability Assay	0.1-1000 nM	72 h		inhibits cell viability dose dependently	25590805
MV411	Apoptosis Assay	30/80/150/250 nM	24/48/72 h		induces dose dependant induction of apoptosis	25882550
HL60	Apoptosis Assay	30/80/150/250 nM	24/48/72 h		induces dose dependant induction of apoptosis	25882550
TC32	qHTS assay				qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for TC32 cells	29435139
A673	qHTS assay				qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for A673 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
SK-N-SH	qHTS assay				qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SK-N-SH 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
A673	qHTS assay				qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for A673 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
Rh18	qHTS assay				qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh18 cells	29435139
Clicca per visualizzare più dati sperimentali sulle linee cellulari

Informazioni chimiche, conservazione e stabilità (Chemical Information, Storage & Stability)

Peso molecolare	364.4	Formula	C₂₀H₂₀N₄O₃	Conservazione (Dalla data di ricezione)	3 anni-20°Cpolvere
N. CAS	888216-25-9	Scarica SDF		Conservazione delle soluzioni stock	1 anno-80°Cin solvente 1 mese-20°Cin solvente
Sinonimi	N/A			Smiles	CC(C)C1=C(C=C(C(=C1)C2=NNC(=O)N2C3=CC4=C(C=C3)N(C=C4)C)O)O

Solubilità (Solubility)

In vitro
Lotto:

DMSO : 40 mg/mL (109.76 mM)
(Il DMSO contaminato da umidità può ridurre la solubilità. Utilizzare DMSO fresco e anidro.)

Ethanol : 9 mg/mL

Water : Insoluble

Calcolatore di Molarità

Massa	Concentrazione	Volume	Peso molecolare
=	×	×

Calcolatore di Diluizione Calcolatore del Peso Molecolare

In vivo Lotto:
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 Validato dai laboratori Selleck. Se necessiti di modifiche a questa formulazione, contatta il nostro team di vendita per test personalizzati.	5.000mg/ml (13.72mM)	Taking the 1 mL working solution as an example, add 50 μL of 100 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.
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.

Calcolatore di formulazione in vivo (Soluzione chiara)

Passo 1: Inserire le informazioni di seguito (Consigliato: Un animale aggiuntivo per tenere conto della perdita durante l'esperimento)

Dosaggio: mg/kg Peso medio degli animali: g Volume di dosaggio per animale:μL Numero di animali:

Passo 2: Inserire la formulazione in vivo (Questo è solo il calcolatore, non la formulazione. Contattateci prima se non c'è una formulazione in vivo nella sezione Solubilità.)

% DMSO + % + % Tween 80 + % ddH₂O

%DMSO+ %

Risultati del calcolo:

Concentrazione di lavoro: mg/ml;

Metodo per preparare il liquido master di DMSO: mg farmaco predissolto in μL DMSO ( Concentrazione del liquido master mg/mL, Vi preghiamo di contattarci prima se la concentrazione supera la solubilità del DMSO del lotto del farmaco. )

Metodo per preparare la formulazione in vivo: Prendere μL DMSO liquido master, quindi aggiungereμL PEG300, mescolare e chiarire, quindi aggiungereμL Tween 80, mescolare e chiarire, quindi aggiungere μL ddH₂O, mescolare e chiarire.

Metodo per preparare la formulazione in vivo: Prendere μL DMSO liquido master, quindi aggiungere μL Olio di mais, mescolare e chiarire.

Nota: 1. Si prega di assicurarsi che il liquido sia limpido prima di aggiungere il solvente successivo.
2. Assicurarsi di aggiungere il/i solvente/i in ordine. È necessario assicurarsi che la soluzione ottenuta, nell'aggiunta precedente, sia una soluzione limpida prima di procedere all'aggiunta del solvente successivo. Metodi fisici come il vortex, gli ultrasuoni o il bagno d'acqua calda possono essere utilizzati per facilitare la dissoluzione.

Meccanismo d'azione (Mechanism of Action)

Targets/IC₅₀/Ki	HSP90 (OSA 8 cells) 4 nM
In vitro	The 50% inhibitory concentrations (IC50) for Ganetespib (STA-9090) against malignant mast cell lines are 10-50 times lower than that for 17-AAG, indicating that triazolone class of HSP90 inhibitors likely exhibits greater potency than geldanamycin based inhibitors. This compound inhibits MG63 cell lines with IC50 of 43 nM. It binds to the ATP-binding domain at the N-terminus of Hsp90 and serves as a potent Hsp90 inhibitor by causing degradation of multiple oncogenic Hsp90 client proteins including HER2/neu, mutated EGFR, Akt, c-Kit, IGF-1R, PDGFRα, Jak1, Jak2, STAT3, STAT5, HIF-1α, CDC2 and c-Met as well as Wilms' tumor 1. At low nanomolar concentrations, it potently arrests cell proliferation and induces apoptosis in a wide variety of human cancer cell lines, including many receptor tyrosine kinase inhibitor- and tanespimycin-resistant cell lines. It exhibits potent cytotoxicity in a range of solid and hematologic tumor cell lines, including those that express mutated kinases that confer resistance to small-molecule tyrosine kinase inhibitors. Its treatment rapidly caused the degradation of known Hsp90 client proteins, exhibits superior potency to the ansamycin inhibitor 17-AAG, and shows sustained activity even with short exposure times. In anohter study, it induces apoptosis of malignant canine mast cell lines. It is active at significantly lower concentrations for C2 and BR canine malignant mast cells with IC50 of 19 and 4 nM, respectively, while 17-AAG inhibits C2 and BR canine malignant mast cells with IC50 of 958 and 44 nM, respectively. Both the expression of WT and mutant Kit are downregulated by 100 nM of this compound after 24 hours in all lines treated including C2 and BMCMCs cells. However, no effects on PI3K or HSP90 expression are observed following treatment with it.
In vivo	Administration of Ganetespib (STA-9090) leads to significant tumor shrinkage in several tumor xenograft models in mice and appears to be less toxic. Furthermore, this compound demonstrated better tumor penetration compared with tanespimycin. It inhibits in vivo tumor growth in both malignant mast cell and OSA xenograft models. Ganetespib significantly inhibits tumor growth when dosed with two repeating cycles of 25 mg/kg/day for 3 days, with a %T/C value of 18. It is well-tolerated, with the vehicle and Ganetespib groups having average bodyweight changes relative to the start of the study of +0.3% and -8.1% on day 17, respectively.
Riferimenti	[1] https://pubmed.ncbi.nlm.nih.gov/19544563/ [2] https://pubmed.ncbi.nlm.nih.gov/21154128/ [3] https://pubmed.ncbi.nlm.nih.gov/22144665/ [4] https://pubmed.ncbi.nlm.nih.gov/18657349/

Applicazioni (Applications)

Metodi	Biomarcatori	Immagini	PMID
Western blot	EGFR / c-Met / IGF-1Rβ/ Akt / p-Akt / ERK / p-ERK p27(Kip1) / p21 (Cip1) / Cyclin D1 / Cyclin E / Cyclin B1 / CDK1 / CDK2 / CDK4 Survivin / Bcl-2 / Bcl-xl / Mcl-1 B-RAF / C-RAF / N-RAS HER2 / p-STAT3 / BIM CDK1 / Cyclin D1 / Cyclin B1 / p27 c-PARP / c-caspase 3 / caspase 8 / c-caspase 8 / caspase 9 / c-caspase 9 ErbB2 / pErbB2 / Src / pSrc / mTOR / pmTOR / Bad / pBad / GSK3 / pGSK3 Wee1 / p-Wee1 / Chk1 / p-Chk1		23418523
Growth inhibition assay	Cell viability		23418523

Informazioni sullo studio clinico (Clinical Trial Information)

(dati da https://clinicaltrials.gov, aggiornato il 2024-05-22)

Numero NCT	Reclutamento	Condizioni	Sponsor/Collaboratori	Data di inizio	Fasi
NCT02192541	Terminated	Neoplasms	National Cancer Institute (NCI)\|National Institutes of Health Clinical Center (CC)	December 2 2014	Phase 1
NCT02008877	Completed	Malignant Peripheral Nerve Sheath Tumors (MPNST)\|Sarcoma	Sarcoma Alliance for Research through Collaboration\|Synta Pharmaceuticals Corp.\|United States Department of Defense	December 2013	Phase 1\|Phase 2

Domande Frequenti (Frequently Asked Questions)

Domanda 1:
Does this inhibitor inhibit both isoforms of HSP90?

Risposta:
We don't have the information now and it is not very clear in the literature either. From following two references, it indicates that it might be specific to the alpha form “It binds to the ATP binding site of Hsp90 alpha with a Kd of 110 nM” http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3477583/

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):