GGTI-2154 is a potent and selective inhibitor of geranylgeranyltransferase I (GGTase I), with an IC₅₀ of 21 nM. GGTI-2154 shows more than 200-fold selectivity for GGTase I over FTase (IC50=5600 nM). GGTI-2154 can be used for the research of cancer^[1][2].

IC50: 21 nM (GGTase I)^[1]

GGTI-2154 inhibits the transfer of geranylgeranyl from [³H]GGPP to H-Ras CVLL, with an IC₅₀ of 21 nM^[1].

Shanghai Jinpan Biotech Co Ltd has not independently confirmed the accuracy of these methods. They are for reference only.

GGTI-2154 (100 mg/kg/day; s.c. for 14 days) induces breast tumor regression in MMTV-ν-Ha-Ras transgenic mice^[2].
GGTI-2154 (50 mg/kg/day; i.p. for 50 day) inhibits A-549 tumor growth in nude mice by 60%^[1].

Shanghai Jinpan Biotech Co Ltd has not independently confirmed the accuracy of these methods. They are for reference only.

420.50

C₂₄H₂₈N₄O₃

251577-10-3

Room temperature in continental US; may vary elsewhere.

Please store the product under the recommended conditions in the Certificate of Analysis.

• [1]. Sun J, et, al. Antitumor efficacy of a novel class of non-thiol-containing peptidomimetic inhibitors of farnesyltransferase and geranylgeranyltransferase I: combination therapy with the cytotoxic agents cisplatin, Taxol, and gemcitabine. Cancer Res. 1999 Oct 1;59(19):4919-26.

  [2]. Sun J, et, al. Geranylgeranyltransferase I inhibitor GGTI-2154 induces breast carcinoma apoptosis and tumor regression in H-Ras transgenic mice. Cancer Res. 2003 Dec 15;63(24):8922-9.

GGTI-2154 is a potent and selective inhibitor of geranylgeranyltransferase I (GGTase I), with an IC₅₀ of 21 nM. GGTI-2154 shows more than 200-fold selectivity for GGTase I over FTase (IC50=5600 nM). GGTI-2154 can be used for the research of cancer^[1][2].

IC50: 21 nM (GGTase I)^[1]

GGTI-2154 inhibits the transfer of geranylgeranyl from [³H]GGPP to H-Ras CVLL, with an IC₅₀ of 21 nM^[1].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

GGTI-2154 (100 mg/kg/day; s.c. for 14 days) induces breast tumor regression in MMTV-ν-Ha-Ras transgenic mice^[2].
GGTI-2154 (50 mg/kg/day; i.p. for 50 day) inhibits A-549 tumor growth in nude mice by 60%^[1].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

420.50

C₂₄H₂₈N₄O₃

251577-10-3

Room temperature in continental US; may vary elsewhere.

Please store the product under the recommended conditions in the Certificate of Analysis.

• [1]. Sun J, et, al. Antitumor efficacy of a novel class of non-thiol-containing peptidomimetic inhibitors of farnesyltransferase and geranylgeranyltransferase I: combination therapy with the cytotoxic agents cisplatin, Taxol, and gemcitabine. Cancer Res. 1999 Oct 1;59(19):4919-26.

  [2]. Sun J, et, al. Geranylgeranyltransferase I inhibitor GGTI-2154 induces breast carcinoma apoptosis and tumor regression in H-Ras transgenic mice. Cancer Res. 2003 Dec 15;63(24):8922-9.

GGTI-2154 is a potent and selective inhibitor of geranylgeranyltransferase I (GGTase I), with an IC₅₀ of 21 nM. GGTI-2154 shows more than 200-fold selectivity for GGTase I over FTase (IC50=5600 nM). GGTI-2154 can be used for the research of cancer^[1][2].

IC50: 21 nM (GGTase I)^[1]

GGTI-2154 inhibits the transfer of geranylgeranyl from [³H]GGPP to H-Ras CVLL, with an IC₅₀ of 21 nM^[1].

Shanghai Jinpan Biotech Co Ltd has not independently confirmed the accuracy of these methods. They are for reference only.

GGTI-2154 (100 mg/kg/day; s.c. for 14 days) induces breast tumor regression in MMTV-ν-Ha-Ras transgenic mice^[2].
GGTI-2154 (50 mg/kg/day; i.p. for 50 day) inhibits A-549 tumor growth in nude mice by 60%^[1].

Shanghai Jinpan Biotech Co Ltd has not independently confirmed the accuracy of these methods. They are for reference only.

420.50

C₂₄H₂₈N₄O₃

251577-10-3

Room temperature in continental US; may vary elsewhere.

Please store the product under the recommended conditions in the Certificate of Analysis.

• [1]. Sun J, et, al. Antitumor efficacy of a novel class of non-thiol-containing peptidomimetic inhibitors of farnesyltransferase and geranylgeranyltransferase I: combination therapy with the cytotoxic agents cisplatin, Taxol, and gemcitabine. Cancer Res. 1999 Oct 1;59(19):4919-26.

  [2]. Sun J, et, al. Geranylgeranyltransferase I inhibitor GGTI-2154 induces breast carcinoma apoptosis and tumor regression in H-Ras transgenic mice. Cancer Res. 2003 Dec 15;63(24):8922-9.

GGTI-2418 is a highly potent, competitive, and selective geranylgeranyltransferase I (GGTase I) inhibitor. GGTI-2418 inhibits GGTase I and FTase activities with IC₅₀s of 9.5 nM and 53 μM, respectively. GGTI-2418 also increases p27(Kip1) and induces significant regression of breast tumors^[1].

IC50: 9.5 nM (GGTase I), 53 μM (FTase)^[1]

GGTI-2418 inhibits GGTase I and FTase activities with IC₅₀s of 9.5±2.0 nM and 53±11 μM, respectively, a 5,600-fold selectivity toward inhibition of GGTase I versus FTase. GGTI-2418 demonstrates competitive inhibition of GGTase I against the H-Ras-CVLL protein with a K_i of 4.4±1.6 nM^[1].
GGTi-2418 (10-15 μM; 16 hours) treatment delocalizes FBXL2 and stabilizes IP3R3^[2].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

GGTI-2418 (100 mg/kg daily or 200 mg/kg every third day; 15 days) significantly inhibits the growth of breast tumor xenografts in nude mice with MDA-MB-231 xenografts^[1].
GGTI-2418 (100 mg/kg daily; 5 days) induces regression of ErbB2-driven mammary tumors in ErbB2 transgenic mice^[1].
GGTI-2418 inhibits the geranylgeranylation of Rap1 and causes a dramatic decrease in S473 phosphorylation of Akt. GGTI-2418 also upregulates p27 levels in vivo^[1].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

441.52

C₂₃H₃₁N₅O₄

501010-06-6

Room temperature in continental US; may vary elsewhere.

DMSO : 125 mg/mL (283.11 mM; Need ultrasonic)

请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。
储备液的保存方式和期限：-80°C, 6 months; -20°C, 1 month。-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。

请根据您的实验动物和给药方式选择适当的溶解方案。以下溶解方案都请先按照 In Vitro 方式配制澄清的储备液，再依次添加助溶剂：

——为保证实验结果的可靠性，澄清的储备液可以根据储存条件，适当保存；体内实验的工作液，建议您现用现配，当天使用； 以下溶剂前显示的百
分比是指该溶剂在您配制终溶液中的体积占比；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的方式助溶

• 1.

  请依序添加每种溶剂： 10% DMSO    40% PEG300    5% Tween-80    45% saline

  Solubility: ≥ 2.08 mg/mL (4.71 mM); Clear solution

  此方案可获得 ≥ 2.08 mg/mL (4.71 mM，饱和度未知) 的澄清溶液。

  以 1 mL 工作液为例，取 100 μL 20.8 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀；向上述体系中加入50 μL Tween-80，混合均匀；然后继续加入 450 μL生理盐水定容至 1 mL。

  将 0.9 g 氯化钠，完全溶解于 100 mL ddH₂O 中，得到澄清透明的生理盐水溶液

• 2.

  请依序添加每种溶剂： 10% DMSO    90% (20% SBE-β-CD in saline)

  Solubility: ≥ 2.08 mg/mL (4.71 mM); Clear solution

  此方案可获得 ≥ 2.08 mg/mL (4.71 mM，饱和度未知) 的澄清溶液。

  以 1 mL 工作液为例，取 100 μL 20.8 mg/mL 的澄清 DMSO 储备液加到 900 μL 20% 的 SBE-β-CD 生理盐水水溶液中，混合均匀。

  将 2 g 磺丁基醚 β-环糊精加入 5 mL 生理盐水中，再用生理盐水定容至 10 mL，完全溶解，澄清透明
• 3.

  请依序添加每种溶剂： 10% DMSO    90% corn oil

  Solubility: ≥ 2.08 mg/mL (4.71 mM); Clear solution

  此方案可获得 ≥ 2.08 mg/mL (4.71 mM，饱和度未知) 的澄清溶液，此方案不适用于实验周期在半个月以上的实验。

  以 1 mL 工作液为例，取 100 μL 20.8 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中，混合均匀。

• [1]. Kazi A, et al. Blockade of protein geranylgeranylation inhibits Cdk2-dependent p27Kip1 phosphorylation on Thr187 and accumulates p27Kip1 in the nucleus: implications for breast cancer therapy. Mol Cell Biol. 2009 Apr;29(8):2254-63.

  [2]. Kuchay S, et al. PTEN counteracts FBXL2 to promote IP3R3- and Ca²⁺-mediated apoptosis limiting tumour growth. Nature. 2017 Jun 22;546(7659):554-558.

GGTI298 is a CAAZ peptidomimetic geranylgeranyltransferase I (GGTase I) inhibitor, strongly inhibiting the processing of geranylgeranylated Rap1A with little effect on processing of farnesylated Ha-Ras, with IC₅₀ values of 3 and > 20 μM in vivo, respectively.

IC50: 3 μM (Rap1A, in vivo), > 20 μM (Ha-Ras, in vivo)^[3]

Both RhoA inhibitor (GGTI298) and ROCK inhibitor (H1152) significantly reduce cAMP agonist-stimulated IK(ap), whereas the latter additionally reduces colocalization of KCNN4c with the apical membrane marker wheat germ agglutinin in T84WT cells^[1]. Knockdown of DR4 abolishes NF-κB activation, leading to sensitization of DR5-dependent apoptosis induced by the combination of GGTI298 and TRAIL. GGTI298/TRAIL activates NF-κB and inhibits Akt. knockdown of DR5, preventes GGTI298/TRAIL-induced IκBα and p-Akt reduction, suggesting that DR5 mediates reduction of IκBα and p-Akt induced by GGTI298/TRAIL. In contrast, DR4 knockdown further facilitates GGTI298/TRAIL-induced p-Akt reduction^[2].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

The vivo mouse ileal loop experiments show fluid accumulation is reduced in a dose-dependent manner by TRAM-34, GGTI298, or H1152 when injected together with cholera toxin into the loop^[1].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

479.63

C₂₇H₃₃N₃O₃S

180977-44-0

Room temperature in continental US; may vary elsewhere.

DMSO : 100 mg/mL (208.49 mM; Need ultrasonic)

请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。
储备液的保存方式和期限：-80°C, 6 months; -20°C, 1 month。-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。

请根据您的实验动物和给药方式选择适当的溶解方案。以下溶解方案都请先按照 In Vitro 方式配制澄清的储备液，再依次添加助溶剂：

——为保证实验结果的可靠性，澄清的储备液可以根据储存条件，适当保存；体内实验的工作液，建议您现用现配，当天使用； 以下溶剂前显示的百
分比是指该溶剂在您配制终溶液中的体积占比；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的方式助溶

• 1.

  请依序添加每种溶剂： 10% DMSO    40% PEG300    5% Tween-80    45% saline

  Solubility: ≥ 2.5 mg/mL (5.21 mM); Clear solution

  此方案可获得 ≥ 2.5 mg/mL (5.21 mM，饱和度未知) 的澄清溶液。

  以 1 mL 工作液为例，取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀；向上述体系中加入50 μL Tween-80，混合均匀；然后继续加入 450 μL生理盐水定容至 1 mL。

  将 0.9 g 氯化钠，完全溶解于 100 mL ddH₂O 中，得到澄清透明的生理盐水溶液

• 2.

  请依序添加每种溶剂： 10% DMSO    90% (20% SBE-β-CD in saline)

  Solubility: 2.5 mg/mL (5.21 mM); Suspended solution; Need ultrasonic

  此方案可获得 2.5 mg/mL (5.21 mM) 的均匀悬浊液，悬浊液可用于口服和腹腔注射。

  以 1 mL 工作液为例，取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 900 μL 20% 的 SBE-β-CD 生理盐水水溶液中，混合均匀。

  将 2 g 磺丁基醚 β-环糊精加入 5 mL 生理盐水中，再用生理盐水定容至 10 mL，完全溶解，澄清透明
• 3.

  请依序添加每种溶剂： 10% DMSO    90% corn oil

  Solubility: ≥ 2.5 mg/mL (5.21 mM); Clear solution

  此方案可获得 ≥ 2.5 mg/mL (5.21 mM，饱和度未知) 的澄清溶液，此方案不适用于实验周期在半个月以上的实验。

  以 1 mL 工作液为例，取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中，混合均匀。

• [1]. Sheikh IA, et al. The Epac1 signaling pathway regulates Cl- secretion via modulation of apical KCNN4c channels in diarrhea. J Biol Chem. 2013 Jul 12;288(28):20404-15

  [2]. Chen S, et al. Dissecting the roles of DR4, DR5 and c-FLIP in the regulation of geranylgeranyltransferase I inhibition-mediated augmentation of TRAIL-induced apoptosis. Mol Cancer. 2010 Jan 29;9:23.

  [3]. McGuire TF, et al. Platelet-derived growth factor receptor tyrosine phosphorylation requires protein geranylgeranylation but not farnesylation. J Biol Chem. 1996 Nov 1;271(44):27402-7.

The given cells are lysed with Reporter Lysis Buffer and subjected to luciferase activity assay using Luciferase Assay System in a luminometer. Relative luciferase activity is normalized to protein content.

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

Cells are seeded in 96-well cell culture plates and treated the next day with the agents indicated. The viable cell number is determined using the sulforhodamine B assay.

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

The ileal loop experiment is performed in 6-8-week-old mice by a modified rabbit ileal loop assay. Following gut sterilization, the animals are kept fasted for 24 h prior to surgery and fed only water ad libitum. Anesthesia is induced by a mixture of ketamine (35 mg/kg of body weight) and xylazine (5 mg/kg of body weight). A laparotomy is performed, and the experimental loops of 5-cm length are constricted at the terminal ileum by tying with non-absorbable silk. The following fluids are instilled in each loop by means of a tuberculin syringe fitted with a disposable needle through the ligated end of the loop as the ligatured is tightened: pure CT (1 μg; positive control), saline (negative control), CT (1 μg) + TRAM-34 (different concentrations in μM as indicated in Fig. 7), CT (1 μg) + H1152 (1 μM), and CT (1 μg) + GGTI298 (different concentrations in μM), a specific inhibitor of Rap1A. The intestine is returned to the peritoneum, and the mice are sutured and returned to their cages. After 6 h, these animals are sacrificed by cervical dislocation, and the loops are excised. The fluid from each loop is collected, and the ratio of the amount of fluid contained in the loop with respect to the length of the loop (fluid accumulation ratio in g/cm) is calculated as a reflection of the efficacy of various inhibitors.

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

• [1]. Sheikh IA, et al. The Epac1 signaling pathway regulates Cl- secretion via modulation of apical KCNN4c channels in diarrhea. J Biol Chem. 2013 Jul 12;288(28):20404-15

  [2]. Chen S, et al. Dissecting the roles of DR4, DR5 and c-FLIP in the regulation of geranylgeranyltransferase I inhibition-mediated augmentation of TRAIL-induced apoptosis. Mol Cancer. 2010 Jan 29;9:23.

  [3]. McGuire TF, et al. Platelet-derived growth factor receptor tyrosine phosphorylation requires protein geranylgeranylation but not farnesylation. J Biol Chem. 1996 Nov 1;271(44):27402-7.