bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract B025: Purine biosynthesis regulates mTORC1 by modulating Rheb GTPase activity
Authors: Unsal-Kacmaz Kezi , Emmanuel Natasha , Ragunathan Shoba , Shan Qin , Wang Fang , Giannakou Andreas , Huser Nanni , Jin Guixian , Myers Jeremy , Abraham Robert T. 
Published: August 2018

Abstract
The mechanistic target of rapamycin complex 1 (mTORC1) regulates protein synthesis through effects on mRNA translation and ribosome biogenesis. Emerging evidence suggests that active mTORC1 also stimulates the de novo biosynthesis of purine and pyrimidine nucleotides. Here, using pharmacologic and genetic tools, we demonstrate that mTORC1 signaling is modulated by cellular purine nucleotide pools arising from the metabolic processes that generate ATP and GTP. Inhibition of GARFT, the enzyme that catalyzes the first folate-dependent step in purine synthesis, by the specific inhibitor AG2037, dramatically inhibits mTORC1 signaling via an AMPK-independent mechanism. GARFT inhibition suppresses the level of the activated form of the Rheb GTPase, a requisite upstream activator of mTORC1, through a global reduction in intracellular guanine-based nucleotides, and subsequently reduces Rheb protein farnesylation. Moreover, we demonstrate that mTORC1 blockade resulting from AG2037-mediated inhibition of GARFT impacts both translation initiation and pyrimidine biosynthesis and results in robust tumor growth inhibition of non-small cell lung cancer (NSCLC) xenografts. Our findings indicate that the regulatory relationship between mTORC1 activity and purine nucleotide pool is bidirectional, and suggest that mTORC1 inhibition contributes to the clinically established antiproliferative effects of purine biosynthesis inhibitors in cancer and inflammatory diseases.
Citation Format: Kezi Unsal-Kacmaz, Natasha Emmanuel, Shoba Ragunathan, Qin Shan, Fang Wang, Andreas Giannakou, Nanni Huser, Guixian Jin, Jeremy Myers, Robert T. Abraham. Purine biosynthesis regulates mTORC1 by modulating Rheb GTPase activity [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2017 Oct 26-30; Philadelphia, PA. Philadelphia (PA): AACR; Mol Cancer Ther 2018;17(1 Suppl):Abstract nr B025.
Abstract B038: Anaplastic lymphoma kinase addicted neuroblastoma cell lines are associated with growth upon treatment with MEK inhibitor trametinib
Authors: Hallberg Bengt , Umapathy Ganesh , Cervantes-Madrid Diana , Guan Jikui , Gustafsson Dan E. , Palmer Ruth H. 
Published: August 2018

Abstract
The RAS-RAF-MEK-ERK pathway is a major player in initiation and progression of multiple cancers where it can be hyper-activated by upstream regulatory proteins, such as tyrosine kinases, phosphatases, and GTPases. Several inhibitors targeting the RAS-MAPK pathway exhibit anticancer activity and are approved as single agent in specific cancers. One such is the MEK inhibitor trametinib, which is included as a rational poly therapy strategy for treating EML4-ALK, EGFR, and K-RAS mutant lung cancer and neuroblastoma containing hyper-activating RAS-MAPK pathway mutations. In neuroblastoma, a heterogeneous disease, relapse cases display an increased rate of mutations of ALK, NRAS, NF1 genes, leading to hyper-activation of RAS-MAPK signaling. Targeting the RAS-MAPK pathways offers attractive options for combinatorial treatment together with ALK inhibitors, since monotreatment has not yet produced strong clinical results in ALK-positive neuroblastoma patients. Here we investigate the response of ALK-positive neuroblastoma cell lines to MEK inhibition, employing trametinib. We show that pharmacologic inhibition of the MEK-ERK pathway in ALK-positive neuroblastoma cells results in increased levels of activation/phosphorylation of AKT and ERK5. This feedback response is regulated by the mTORC2 complex protein SIN1. Taken together, our results indicate that blocking MEK-ERK leads to "increased activation" of AKT signalling core in ALK-positive neuroblastoma, intensifying survival signals in these cells. Our results contraindicate use of MEK inhibitors as effective single and poly-therapeutic strategy in ALK-positive neuroblastoma.
Citation Format: Bengt Hallberg, Ganesh Umapathy, Diana Cervantes-Madrid, Jikui Guan, Dan E. Gustafsson, Ruth H. Palmer. Anaplastic lymphoma kinase addicted neuroblastoma cell lines are associated with growth upon treatment with MEK inhibitor trametinib [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2017 Oct 26-30; Philadelphia, PA. Philadelphia (PA): AACR; Mol Cancer Ther 2018;17(1 Suppl):Abstract nr B038.
Abstract B043: Mithramycin-SA analogues with reduced toxicity for the treatment of ETS transcription factor-driven tumors
Authors: Leggas Markos , Eckenrode Joseph , Mitra Prithiba , Jha Amit , Salem Shaimaa , Mandal Abhisek , Thorson Jon , Rohr Jurgen 
Published: August 2018

Abstract
Introduction: Chromosomal translocations involving the ETS family of transcription factors are common in Ewing sarcoma, prostate cancer, and leukemia. These translocations lead in overexpression of aberrant ETS transcription factors, which drive tumorigenesis. Mithramycin (MTM) inhibits EWS-FLI1, the most common ETS-related transcription factor in Ewing sarcoma, presumably through interference at its DNA binding sites on promoter regions. However, MTM has a narrow therapeutic window marked by severe liver and hematologic toxicities. These are likely the result of interference with the ubiquitously expressed SP1 transcription factor. Here, we sought to develop analogues with specificity toward ETS transcription factors and reduced interaction with SP1. Methods: Using MTM-SA and semisynthetic approaches a series of analogues were obtained. To determine specificity toward cells expressing ETS-related chromosomal translocations, MTM-SA analogues were screened for growth inhibition in a panel of Ewing sarcoma cell lines (n=8), all expressing EWS-ETS translocations, and compared to a panel of non-Ewing cell lines (n=9) that do not express these translocations. Luciferase reporter constructs were developed to evaluate interference with EWS-FLI1 and SP1 regulated genes following MTM-SA analogue treatment. Select analogues were tested in vivo to identify the maximum tolerated dose and determine pharmacokinetics (PK). Results: In growth inhibition assays, several MTM-SA analogues resulted in &gt; 10-fold specificity toward Ewing sarcoma cell lines vs. MTM. Luciferase reporter assays identified two analogues, MTM-SA-Tryptophan-A2 and MTM-SA-Tryptophan-A10, with 10-fold reduced inhibition of SP1 but similar inhibition of EWS-FLI1, as compared to MTM. Additionally, MTM-SA-Phe analogue has lower toxicity, despite longer plasma half-life. Conclusion: These data show that MTM-SA analogues are cytotoxic against tumor cell lines expressing aberrant ETS transcription factors. Further, their reduced interference with the ubiquitously expressed SP1 transcription factor, as well as their improved PK, may result in a wider therapeutic window.
Citation Format: Markos Leggas, Joseph Eckenrode, Prithiba Mitra, Amit Jha, Shaimaa Salem, Abhisek Mandal, Jon Thorson, Jurgen Rohr. Mithramycin-SA analogues with reduced toxicity for the treatment of ETS transcription factor-driven tumors [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2017 Oct 26-30; Philadelphia, PA. Philadelphia (PA): AACR; Mol Cancer Ther 2018;17(1 Suppl):Abstract nr B043.
Abstract B060: Small molecule inhibitor of pre-mRNA splicing evokes antitumor activity via MDM4-p53 pathway
Authors: Nishimura Kazuho , Yaguchi Masahiro , Yamamoto Yukiko , Ebara Shunsuke , Yoichi Kawakita , Mizojiri Ryo , Nakayama Yusuke , Hayashi Kozo , Miyakawa Shuichi , Iwai Kenichi , Nomura Toshiyuki 
Published: August 2018

Abstract
Proper control of gene expression at the level of transcription and RNA processing is a fundamental process of tumor cell growth. Here we showed that a novel pre-mRNA splicing modulator, Cdc2-like kinase (CLK) inhibitor T-025, suppressed tumor cell growth in vitro and in vivo. To reveal the mechanisms linking aberrant splicing and tumor growth suppression by T-025, we combined transcriptomic RNA-seq and proteomic p-SILAC data. We identified MDM4 as a mediator for triggering p53-dependent apoptosis in response to T-025. CLK inhibition led to exon 6 skipping of MDM4 mRNA, a potential target for nonsense-mediated decay, decreasing MDM4 protein. Consistent with these results, overexpression of MDM4 or knockdown of p53 attenuated growth-suppressive effects of T-025. We then investigated the relationship between genomic features and sensitivity to T-025 by evaluating the antiproliferative effect of T-025 against 240 cancer cell lines. Strikingly, expression of MDM4 was correlated with that of CLK2 and cell sensitivity to T-025. In addition, we found that copy number variation and mRNA expression of MYC were correlated with cell sensitivity to T-025. T-025 exhibited greater sensitivity in MYC-expressing cells and MYC-driven spontaneous breast cancer models. Together, we demonstrated that MDM4-p53 signaling and MYC-activation have key roles in antitumor activity of CLK inhibitor.
Citation Format: Kazuho Nishimura, Masahiro Yaguchi, Yukiko Yamamoto, Shunsuke Ebara, Kawakita Yoichi, Ryo Mizojiri, Yusuke Nakayama, Kozo Hayashi, Shuichi Miyakawa, Kenichi Iwai, Toshiyuki Nomura. Small molecule inhibitor of pre-mRNA splicing evokes antitumor activity via MDM4-p53 pathway [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2017 Oct 26-30; Philadelphia, PA. Philadelphia (PA): AACR; Mol Cancer Ther 2018;17(1 Suppl):Abstract nr B060.
Abstract B071: Detecting ultra low-frequency variants and fusions using a novel amplicon-based Accu-CometTM method
Authors: Wang Ling , Zhao Grace Q. , Weng Li , Chen Xiao , Li Min , Yang Xue , Zhao Jun , Wang Hongyan , Ying Kang , Faham Malek , Lin Shengrong , Lou Jiatao 
Published: August 2018

Abstract
We report the development of an ultra-accurate NGS technology, Accu-CometTM, which employs a concatemer-based error correction with amplicon workflow for the fast detection of low-frequency mutations including single-nucleotide variants (SNVs) and fusion events. We tested a non-small cell lung cancer (NSCLC) panel covering variants of EGFR, BRAF, and KRAS, as well as Alk fusion. Simulated cfDNA and cfDNA from healthy individuals were used to test the assay’s sensitivity and specificity. The analytic sensitivity of this panel was 100% detection at an allele frequency of 0.1% for 20ng of cf-DNA input. Similarly, the analytic sensitivity of the Alk fusion panel was 75% detection at an allele frequency of 0.1%, and 100% detection at an allele frequency of 0.25% for the same input. Clinical validation was performed via a comparative analysis of 171 NSCLC patients at different cancer stages and with different treatment plans. Among our patient cohort, 5 EGFR variants (19del, T790M, L858R, G719X, L861X) were detected. We also tested 47 noncancerous control samples and detected no false-positive variants at the reported cancer hot spots. Accu-CometTM demonstrated strong per-variant detection-rate concordance (&gt; 96%) compared to ddPCR results, and &gt;90% concordance when compared to tumor tissue ARMS result. The multiplex capacity, ultra sensitivity, and easy robust work flow of Accu-CometTM makes it well suited for supporting targeted therapy selection, drug resistance detection, and treatment monitoring.
Citation Format: Ling Wang, Grace Q. Zhao, Li Weng, Xiao Chen, Min Li, Xue Yang, Jun Zhao, Hongyan Wang, Kang Ying, Malek Faham, Shengrong Lin, Jiatao Lou. Detecting ultra low-frequency variants and fusions using a novel amplicon-based Accu-CometTM method [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2017 Oct 26-30; Philadelphia, PA. Philadelphia (PA): AACR; Mol Cancer Ther 2018;17(1 Suppl):Abstract nr B071.
Abstract B096: canSAR, a cancer research and drug discovery knowledgebase
Authors: Coker Elizabeth A. , Di Micco Patrizio , Tym Joesph E. , Mitsopoulos Costas , Komianou Angeliki , Antolin Albert A. , Al-Lazikani Bissan 
Published: August 2018

Abstract
canSAR (http://cansar.icr.ac.uk) is a freely available, multidisciplinary, cancer-focused knowledgebase developed to bring together information from genomic, transcriptomic, protein, pathway, chemical, pharmacologic, and 3D structural data. canSAR provides a powerful, uniqu,e and user-friendly portal to enable translational research and to help generate and test hypotheses and support scientific decision-making in drug discovery both before and after target selection. With its three alternative approaches to examine druggability, canSAR represents the most comprehensive public druggability assessment resource. canSAR provides 3D-structure-based druggability assessment for more than 3,100,000 cavities on more than 391,000 protein chains; ligand-based druggability assessment for 8,197 human proteins; and, more recently, protein network-based druggability results for 13,345 human proteins. Together these provide a powerful enabler for target selection and validation for drug discovery. Druggability assessments are presented alongside data from resources including 224,000 clinical trials from ClinicalTrials.gov, drug indications from Cancer.gov, target gene expression from TCGA for cell lines, and patient samples to provide a detailed picture of the target’s biologic context. Recent updates to canSAR include integration of ChEMBL 23 and additional curation of a protein-protein interaction network of 13,500 nodes. canSAR is currently used by more than 65,000 users annually from both academia and industry, and we will illustrate how canSAR can empower decision making in translational drug discovery.
Citation Format: Elizabeth A. Coker, Patrizio Di Micco, Joesph E. Tym, Costas Mitsopoulos, Angeliki Komianou, Albert A. Antolin, Bissan Al-Lazikani. canSAR, a cancer research and drug discovery knowledgebase [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2017 Oct 26-30; Philadelphia, PA. Philadelphia (PA): AACR; Mol Cancer Ther 2018;17(1 Suppl):Abstract nr B096.
Abstract B097: Dysregulated mevalonate and cholesterol synthesis is a therapeutic vulnerability in glioblastoma
Authors: Kambach Diane M. , Halim Alan S. , Cauer A. Gesine , Sun Qian , Tristan Carlos A. , Kesarwala Aparna H. , Shankavaram Uma , Batchelor Eric , Stommel Jayne M. 
Published: August 2018

Abstract
A hallmark of cellular transformation is the evasion of contact-dependent inhibition of growth. To find new therapeutic targets for glioblastoma, we looked for pathways that are inhibited by high cell density in normal astrocytes but have lost this regulation in glioblastoma stem-like cells. Here we report that at high cell density, normal astrocytes turn off mevalonate and cholesterol synthesis but glioma cells keep these pathways active. Correspondingly, mevalonate and cholesterol pathway upregulation is associated with poor prognosis in glioblastoma patients. Densely plated glioma cells increase oxygen consumption to synthesize cholesterol, resulting in a decrease in reactive oxygen species, TCA cycle intermediates, and ATP, but without a compensating increase in aerobic glycolysis. This constitutive cholesterol synthesis is controlled by the cell cycle, as it can be turned off by cyclin-dependent kinase inhibitors and it correlates with disabled cell cycle control though loss of p53 and RB. Mevalonate and cholesterol pathway activation promoted aberrant growth through the LXR and Hippo pathways. Finally, glioma cells, but not astrocytes, are sensitive to cholesterol synthesis inhibition downstream of the mevalonate pathway, suggesting that specifically targeting cholesterol synthesis might be an effective treatment for glioblastoma.
Citation Format: Diane M. Kambach, Alan S. Halim, A. Gesine Cauer, Qian Sun, Carlos A. Tristan, Aparna H. Kesarwala, Uma Shankavaram, Eric Batchelor, Jayne M. Stommel. Dysregulated mevalonate and cholesterol synthesis is a therapeutic vulnerability in glioblastoma [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2017 Oct 26-30; Philadelphia, PA. Philadelphia (PA): AACR; Mol Cancer Ther 2018;17(1 Suppl):Abstract nr B097.
Abstract B120: TAK-164, a GCC-targeted antibody-drug conjugate (ADC) for the treatment of colorectal cancers and other GI malignancies
Authors: Abu-Yousif Adnan O. , Bannerman Bret M. , Cvet Donna , Gallery Melissa , Ganno Michelle L. , Smith Michael D. , Lai Katharine C. , Keating Thomas A. , Bolleddula Jayaprakasam , Stringer Bradley , Qian Mark G. , Kamali Afrand , Eng Kurt , Koseoglu Secil , Xia Cindy Q. , Veiby O. Petter 
Published: August 2018

Abstract
TAK-164 is an antibody-drug conjugate comprising a full-length, fully human IgG1 monoclonal antibody (mAb) directed towards the extracellular domain of guanylyl cyclase C (GCC). The mAb is conjugated using the peptide-linked indolino-benzodiazepine DNA alkylator DGN549 (also known as IGN-P1). TAK-164 demonstrates efficient binding to antigen-expressing cells in vitro, and GCC-dependent uptake that results in cytotoxicity. Following a single administration of TAK-164 in female SCID mice bearing GCC-positive xenografts, the pharmacokinetics of the conjugated antibody component of TAK-164 displayed low plasma clearance. Exposure to the ADC resulted in a dose- and time-dependent increase in DNA damage as measured by the pharmacodynamic marker pH2A.X in GCC-positive tumor-bearing xenografts. To further these observations, antitumor activity of TAK-164 was evaluated in multiple GCC-positive patient-derived xenografts. In these studies, a single intravenous administration of TAK-164 resulted in durable antitumor activity. Furthermore, the use of preclinical imaging demonstrated that TAK-164 preferentially accumulates in GCC-positive tumors, and that treatment response can be monitored using FDG-PET. These promising preclinical data warrant advancement of this ADC to clinical evaluation.
Citation Format: Adnan O. Abu-Yousif, Bret M. Bannerman, Donna Cvet, Melissa Gallery, Michelle L. Ganno, Michael D. Smith, Katharine C. Lai, Thomas A. Keating, Jayaprakasam Bolleddula, Bradley Stringer, Mark G. Qian, Afrand Kamali, Kurt Eng, Secil Koseoglu, Cindy Q. Xia, O. Petter Veiby. TAK-164, a GCC-targeted antibody-drug conjugate (ADC) for the treatment of colorectal cancers and other GI malignancies [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2017 Oct 26-30; Philadelphia, PA. Philadelphia (PA): AACR; Mol Cancer Ther 2018;17(1 Suppl):Abstract nr B120.
Abstract B125: A novel BBB-permeable chemotherapeutic agent for the treatment of CNS tumors
Authors: Nicolaides Theodore P. , Ozawa Tomoko , Yao Tsun Wen , Prados Michael , Fischer Wolf-Nicolas , Jandeleit Bernd , Koller Kerry 
Published: August 2018

Abstract
Standard of care for glioblastoma multiforme (GBM) patients is surgical tumor resection, followed by radiation and chemotherapy with temozolomide. Unfortunately, 60% of newly diagnosed GBM patients express high levels of the DNA repair enzyme MGMT and are temozolomide-insensitive, and all patients eventually become refractory to treatment. The blood-brain barrier (BBB) remains an obstacle to adequate delivery of chemotherapeutic agents to brain tumors. Lipophilic drugs such as temozolomide and lomustine are able to cross the BBB based on passive diffusion; however, their tissue distribution also causes toxicity to critical systemic organs, such as the bone marrow, leading to dose-limiting toxicity. Therefore, BBB-permeable chemotherapeutic agents that are efficacious in temozolomide-insensitive and refractory patients are needed. The large amino acid transporter 1 (LAT1) is highly expressed on the BBB and in GBM and other malignant brain tumors such as diffuse intrinsic pontine glioma (DIPG), where it is associated with poor prognosis, but is undetectable in normal brain tissue. Targeting LAT1 transport, while avoiding interaction with other closely related transporters expressed on normal tissue such as LAT2, will target brain tumors and avoid uptake into healthy tissue. We report the generation of a novel molecule (QBS10072S) that combines a potent cytotoxic domain with the structural features of a selective LAT1 substrate. QBS10072S is 50-fold more selective for LAT1 vs. LAT2 in transport assays, and demonstrates significant in vitro cytotoxicity to LAT1-expressing GBM cell lines and minimal cytotoxicity to normal human astrocytes (LAT1-negative). Unlike temozolomide, QBS10072S is cytotoxic to cells with both high and low levels of MGMT expression. In orthotopic glioblastoma xenografts, QBS10072S causes significant delay in tumor growth and increase in mouse survival compared to vehicle. QBS10072S is well tolerated, with no toxicity seen in normal brain or the BBB. In summary, QBS10072S is a novel BBB-permeable chemotherapeutic agent with the potential to treat temozolomide-insensitive and recurrent GBM.
Citation Format: Theodore P. Nicolaides, Tomoko Ozawa, Tsun Wen Yao, Michael Prados, Wolf-Nicolas Fischer, Bernd Jandeleit, Kerry Koller. A novel BBB-permeable chemotherapeutic agent for the treatment of CNS tumors [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2017 Oct 26-30; Philadelphia, PA. Philadelphia (PA): AACR; Mol Cancer Ther 2018;17(1 Suppl):Abstract nr B125.
Abstract B150: ASN007, a novel oral ERK inhibitor, shows robust antitumor activity in RAS mutant cancer models
Authors: Reddy Sanjeeva P. , Sivanandhan Dhanalakshmi , Dewang Purushottam , Rao Niranjan , Smith Roger A. , Thompson Scott K. 
Published: August 2018

Abstract
The extracellular-signal-regulated kinases, ERK1 and ERK2 (ERK1/2), are key players in the RAS/RAF/MEK signaling pathway. This pathway is frequently hyper-activated in a wide range of cancers through mutations in upstream targets such as BRAF, RAS, and receptor tyrosine kinases. Inhibition of ERK1/2 offers a promising therapeutic strategy for these cancers, particularly the ones driven by RAS mutations. In order to inhibit this critical node of the RAS/RAF/MEK pathway, we discovered and characterized ASN007, a novel compound that shows potent inhibition of ERK1/2 kinases in a biochemical assay with low single-digit nM IC50 values. ASN007 showed a slow dissociation rate (long target residence time) as compared to several other known ERK inhibitors. In mechanistic cell-based assays, ASN007 inhibited the phosphorylation of ERK1/2 substrates such as RSK1, FRA1, and Elk1 in various cell lines. ASN007 showed single-digit nanomolar antiproliferative activity that was selective for MAPK-pathway dependent cancer cell lines. Indeed, ASN007 showed much more potent activity against a broader panel of KRAS, NRAS, and HRAS mutant cell lines compared to other ERK1/2 inhibitors such as BVD-523 and GDC-0994. In a daily oral dosing regimen, ASN007 demonstrated strong inhibition of tumor growth in multiple BRAF and KRAS mutant xenograft models in mice and was well tolerated at efficacious doses. Of note, ASN007 also showed strong efficacy using various intermittent dosing regimens. ASN007 has a good pharmacokinetic profile in preclinical species and does not exhibit significant inhibition of CYP enzymes or hERG channel. IND-enabling studies are ongoing in preparation for a phase 1 clinical trial to evaluate oral ASN007 in patients with BRAF and K- , H- , and N-RAS mutant cancers
Citation Format: Sanjeeva P. Reddy, Dhanalakshmi Sivanandhan, Purushottam Dewang, Niranjan Rao, Roger A. Smith, Scott K. Thompson. ASN007, a novel oral ERK inhibitor, shows robust antitumor activity in RAS mutant cancer models [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2017 Oct 26-30; Philadelphia, PA. Philadelphia (PA): AACR; Mol Cancer Ther 2018;17(1 Suppl):Abstract nr B150.