The fight to find effective, long-lasting treatments for cancer has led many researchers to consider protein degrading entities. Recent developments in PROteolysis TArgeting Chimeras (PROTACs) have signified their potential as possible cancer therapies. PROTACs are small molecule, protein degraders that function by hijacking the built-in Ubiquitin-Proteasome pathway. This review mainly focuses on the general design and functioning of PROTACs as well as current advancements in the development of PROTACs as anticancer therapies. Particular emphasis is given to PROTACs designed against various (...) types of Leukemia/Blood malignancies. (shrink)

Abū Ishāq al-Ṣaffār was one of scholars of the Western Qarakhānids’ period who followed the Kalām thought of al-Māturīdī (d. 333/944). His theological works Talkhīs al-adilla and Risāla fī al-kalām, his method in kalām, and frequent reference to his works by Ottoman and Arab scholars indicate that al-Ṣaffār is a respected and authorative Māturīdī theologian. The article focuses on his defense of the kalām. By adding a long introduction to Talkhīs about the naming, importance, and religious legitimacy of the science (...) of kalām, Saffār asserted that the kalām should be learned. When systematical vindication of the science of kalām is examined, it is understood that al-Ṣaffār is the first theologian who reserved a private and voluminous part for defensing the kalām among Ḥanafī-Māturīdīs. Even though he does not state its systematic, it can be understood that vindication of kalām in al-Ṣaffār divides into three parts as of explanation, demonstration and refutation. Al-Ṣaffār’s defending the science of kalām shows that there were opposite thoughts against kalām in the 4th/10th and 5th/11th centuries throughout in Transoxania. In this period Aṣḥāb al-Ḥadīth and Ikhwān al-Ṣafāʾ were the opposite fronts of kalām. In addition, he was trying to go beyond the oppositions of Ḥanafī jurists. His vindication is consistent and has scholarly depth because it is able to be against a strong opposition. -/- SUMMARY: Abū Ishāq Ibrahīm b. Ismāil Zāhid al-Ṣaffār al-Bukhārī is a scholar belonging to the Ḥanafī theological tradition which was improved by the contribution of Ḥanafī theologians who used thinking system of Abū Ḥanīfa (d. 150/767) as base and adopted Abū Manṣūr al-Māturīdī (d. 333/944) and his thoughts in historical process. The contents of his theological works Talkhīs al-adilla li-qawāʿid al-tawḥīd and Risāla fī al-Kalām, the method that he used, and references to his works made by Ottoman and Arab scholars indicate that he is an important Māturīdī theologian. The article focuses on his defense of the science of Kalām. -/- In Talkhīs al-adilla, there are two sections including the subject of naming, and importance and necessity of Kalām discipline. Here, the necessity of learning Kalām and its value are defended in detail. -/- Besides, rumors “Abū Ḥanīfa turned away from the science of Kalām in his doomsdays” and that “He prohibited to make occupation with Kalām completely” are evaluated. -/- When systematical vindication of the science of Kalām is examined, it is understood that al-Ṣaffār is the first theologian who reserved a private and voluminous part for defensing the Kalām among Ḥanafī Māturīdīs. Even if Abū Manṣūr al-Māturīdī, Abū al-Yusr al-Bazdawī (d. 493/1100) and Abū Muʿīn al-Nasafī (d. 508/1115) defend that the science of Kalām is not wrong for religion; yet, the vindication of Kalām does not take a place under a separate title and in a detailed manner in any of Māturīdī theologians works. -/- The method that al-Ṣaffār used when he is defending the science of Kalām, differs from strategy of Abū Ḥanīfa. While Abū Ḥanīfa has mentioned that there is a need for the science of Kalām under these new circumstances, al-Ṣaffār has defended theologians who were charged with being Ahl al-Bidaʿ, by trying to prove that the prophets especially the Prophet Ibrāhīm, even the Companions of the Prophet Muḥammad (Ṣaḥāba) and the Successors of the Companions (Tābiʿūn) scholars use their minds and make arguments in religious matters. In this respect, he emphasizes that the Qurʾān orders to think and discuss gently, not to be stay in silence: “And dispute with them, using what is best” (16.125-126). Therefore, he states that this discipline which took a mission to explain and defend the creed of Islam (ʿaqīda), cannot be characterized as an innovation (bidʿah) or illicit. -/- His vindication method can be defined as a more developed type of method that Abu’l-Ḥasan al-Ash’arī’s (d. 324/935) used in Risāla fī istiḥsān al-khawḍ fī ʿilm al-kalām. Even though he does not state its systematic, it can be understood that vindication of Kalām in al-Ṣaffār divides into three parts as of explanation, demonstration and refutation: -/- a) Explanation: Explaining the necessity and importance of the science of Kalām by giving information about its definition, names, value and place among other principles. -/- b) Demonstration: Revealing the religious basics of the science of Kalām from the Qurʾān, the Sunna of the Prophet Muḥammad, the Companions of the Prophet, and the Successors of the Companions thus specifying that it is legitimate for religion. -/- c) Refutation: Replying the claims having aim to weaken the value of Kalām principle and its religious legality. -/- Al-Ṣaffār describes ‘the science of Kalām’ as ‘Knowing the Real with the evidences which help to reach the absolute information’. By allocating the concept of 'Ḥaqq', he repeats the definition of Kalām as “it is to know God with certain evidences” in a part of his work, and “it is to know the principles of religion (uṣūl al-dīn) with certain evidences” in another part. He describes Kalām as “Knowing ḥaqq / God / uṣūl al-dīn by depending on evidence”, and tries to prove that it is wrong to consider a science which performs the stated duty, as illicit and abominable and thus turn away from it. -/- Al-Ṣaffār thinks that it is right to call this principle as ‘Kalām’ because of the certain evidences leading to the truth that this science has used. This thought was defended by other theologians as well. -/- For example, according to Saʿd al-Dīn Masʿūd al-Taftazānī (d. 792/1310) it seems like to say “This is the word (kalām), not the other knowings” by the way of the power of evidences used in Kalām.Thus, it is appropriate to give name Kalām for this science which based on certain evidences. -/- Al-Ṣaffār’s explanations revealed in scope of vindication of the Kalām are adopted by some of following scholars. Ḥusām al-Dīn al-Sighnāqī (d. 714/1314) in his book called al-Tasdīd sharḥ al-Tamhīd fī qawāʿid al-tawḥīd quotes Saffâr’s explanations as the same. -/- Al-Ṣaffār indicates that the method told in the Qurʾān is to reply questions about religion, beliefs and rejection instead of remaining in silence. The duty taken on by Kalām is this vindication activity performed by the prophets whose examples are described in the Qurʾān and which is legal and demanded. His way of thinking and vindication of the Kalām resembles that of Abū Manṣūr al-Māturīdī. Al-Māturīdī says, “Prophets and we were ordered to invite infidels to Islam. When this invitation happens, the respondents will ask for evidence and explanation, and discussion will be inevitable. Therefore, discussing and talking about subjects of Kalām is not objectionable”. -/- Thoughts of al-Māturīdī and al-Ṣaffār regarding the vindication of the Kalām were repeated by Nūr al-Dīn al-Ṣābūnī (d. 580/1184), and Fakhr al-Dīn al-Rāzī (d. 606/1210) later. According to al-Ṣābūnī, the evidences put against deniers and especially the discussion made by the Prophet Ibrāhīm to defend his own belief, prove the legality of Kalām discipline. Likewise, according to al-Rāzī, the duty of Kalām is just an activity performed already in the Qurʾān and ordered to the prophets. At this point of view, since the prophets were leading to Kalām, banning this activity is nonsense. -/- According to al-Ṣaffār, the reason for why Abu Hanifa avoids his son Hammād from these discussions is that Abu Hanifa does not like discussions based on obstinate. Otherwise, it cannot be that Abū Ḥanīfa prohibits to learn Kalām and make discussion about Kalām. According to him, this behavior of Abū Ḥanīfa results from that people discussing with him are ignorant about the subject of Kalām, discussion turns to an obstinate, and coming to an end of discussion seems impossible. This comment of al-Ṣaffār is quoted in Miftāḥ al-saʿāda wa-miṣbāḥ al-siyāda by ʿIṣām al-Dīn Aḥmed b. Muṣṭafā Tashköprüzāde (d. 968/1561) and in Minaḥ al-rawḍ al-azhar fī sharḥ al-Fiqh al-akbar by ʿAlī b. Sulṭān Muḥammad al-Qārī (d. 1014/1606) as same as his words. -/- Al-Ṣaffār’s defending the science of Kalām shows that there were opposite thoughts against Kalām in the 4th/10th and 5th/11th centuries throughout in Transoxania.In this period Aṣḥāb al-Ḥadīth and Ikhwān al-Ṣafāʾ were the opposite fronts of Kalām. In addition, he was trying to go beyond the oppositions of Ḥanafī jurists (fuqahāʾ). Because some of the Ḥanafī jurists thought that Abū Ḥanīfa forsook occupation with the science of Kalām and even he prohibited his son to have interest in this discipline. But some of Ḥanafī theologians such as al-Māturīdī, al-Nasafī and al-Ṣaffār protested this thought which describes Abū Ḥanīfa as a banner for Kalām. -/- His vindication is consistent and has scholarly depth because it is able to be against a strong opposition. -/- His book Talkhīs al-adilla li-qawāʿid al-tawḥīd is a unique source in terms of containing vindication of the Kalām in detail and also influencing the approaches of the next period scholars. (shrink)