“幾杯啤酒”聊出來的科學(xué)夢(mèng)想，曾被嘲“不切實(shí)際”，近日已有一款新藥成功獲批上市！藥明康德如何助力它們走向前沿？

十多年前，藥明康德收到了一家小型生物技術(shù)公司發(fā)來的研發(fā)需求。讀完資料后，相關(guān)團(tuán)隊(duì)的第一反應(yīng)是“震撼”。這是他們第一次見到分子量如此之大、結(jié)構(gòu)如此“奇特”的分子。

這種奇特的分子，就是后來引起廣泛關(guān)注的蛋白降解靶向嵌合體（Proteolysis Targeting Chimera）療法。

當(dāng)時(shí)，蛋白降解靶向嵌合體和它背后的Arvinas公司，都還沒有得到如今的關(guān)注。以“誘導(dǎo)接近”（induced proximity）為機(jī)理，將致病蛋白“拉近”到細(xì)胞里的E3連接酶，針對(duì)性地進(jìn)行靶向蛋白降解，在整個(gè)行業(yè)里都是一個(gè)比較新的概念，少有研發(fā)賦能平臺(tái)接觸過這樣的化學(xué)結(jié)構(gòu)。

為了更好地滿足客戶的研發(fā)需求、助力客戶早日實(shí)現(xiàn)創(chuàng)新夢(mèng)想，面對(duì)化學(xué)上的挑戰(zhàn)，藥明康德依然毫不猶豫地接受了下來。

這次合作，為藥明康德與Arvinas公司往后10年的攜手同行拉開了序幕。而蛋白降解靶向嵌合體療法在臨床上取得的進(jìn)展，也無形之中影響了靶向蛋白降解這一行業(yè)浪潮的方向。

“幾杯啤酒”聊出來的科學(xué)創(chuàng)想

1998年，美國華盛頓州一個(gè)風(fēng)景如畫的度假村里，一場學(xué)術(shù)會(huì)議正在召開。

在這里，耶魯大學(xué)的克雷格·克魯斯（Craig Crews）教授遇到了他的知音——當(dāng)時(shí)在加州理工學(xué)院任教的雷蒙德·德沙耶（Raymond Deschaies）教授。他們都非常關(guān)注一個(gè)研究方向：如何利用細(xì)胞天然的“蛋白質(zhì)回收系統(tǒng)”治療疾病。

此前已經(jīng)有科學(xué)家發(fā)現(xiàn)，細(xì)胞內(nèi)有一種蛋白復(fù)合體，它的作用就像“回收站”，可以把異常、廢棄的“垃圾蛋白”降解掉。更妙的是，有另外三類酶能通過一系列步驟，給垃圾蛋白“貼上待降解標(biāo)簽”（泛素化處理），這個(gè)標(biāo)簽?zāi)鼙弧盎厥照尽本珳?zhǔn)識(shí)別，從而降解“垃圾蛋白”。三位科學(xué)家因發(fā)現(xiàn)這一“泛素介導(dǎo)的蛋白降解系統(tǒng)”，獲得了2004年的諾貝爾化學(xué)獎(jiǎng)。

▲“帶標(biāo)簽的垃圾蛋白”（左）被“回收站”（右）識(shí)別、降解的過程（圖片來源：參考資料[18]）

那天，德沙耶教授正在聽克魯斯教授講解“如何用小分子把兩個(gè)蛋白質(zhì)連在一起”。當(dāng)時(shí)正一心研究泛素連接酶的他，腦中突然閃過一個(gè)靈感，問道：如果小分子連接的是蛋白質(zhì)與泛素連接酶，是不是可以驅(qū)動(dòng)蛋白質(zhì)的泛素化降解呢？

克魯斯教授頓時(shí)眼前一亮——之前他就想過，很多疾病都有特定的致病蛋白，如果能利用“回收系統(tǒng)”精準(zhǔn)降解致病蛋白就好了。而德沙耶教授提出的觀點(diǎn)，為他冥思苦想而不得解的難題帶來了一條新的解題思路！

順著這個(gè)靈感，兩位科學(xué)家越聊越投入，一邊吃飯，一邊還在討論科學(xué)創(chuàng)想。

“幾杯啤酒下肚，我們就開始‘異想天開’，然后想到了一條新點(diǎn)子。如果能成功，它將會(huì)是一種變革性的新療法！”

兩位科學(xué)家的設(shè)想是：利用誘導(dǎo)接近機(jī)制（通過將蛋白或核酸拉近形成復(fù)合體，從而調(diào)控靶點(diǎn)功能），讓小分子“一只手抓住”（結(jié)合）致病蛋白，“另一只手抓住”泛素連接酶，讓前者靠近后者并被打上“待降解垃圾”的標(biāo)簽，或許就能利用細(xì)胞內(nèi)的“回收站”降解這些有害蛋白。

▲PROTAC?藥物分子設(shè)計(jì)：一頭（左）連上致病蛋白、另一頭（右）連接泛素連接酶，后者給前者“貼標(biāo)簽”（圖片來源：參考資料[18]）

而且他們敏銳地意識(shí)到，相比傳統(tǒng)的小分子抑制劑，這種新分子有不同的優(yōu)勢(shì)。

傳統(tǒng)靶向療法的思路是，讓小分子抑制劑與致病蛋白精準(zhǔn)結(jié)合，就像一把“鑰匙”把致病蛋白的“鎖眼”（活性靶點(diǎn)結(jié)合位點(diǎn)）反鎖起來，讓它無法發(fā)揮致病作用。問題在于，85%的致病蛋白沒有“鎖眼”或不容易找到與之吻合的“鑰匙”，因此被認(rèn)為“難以成藥/不可成藥”；還有一些能“反鎖”成功的“鑰匙”，由于吻合不夠牢固、“鎖眼”變異等問題，時(shí)間久了也會(huì)脫落、失效，即產(chǎn)生了耐藥性。

而他們的新方法繞開了“找鎖眼配鑰匙”的過程，選擇直接把“帶鎖眼的門把手”拆除銷毀，讓這扇“致病之門”無法打開。因此，那些不可成藥和耐藥的難題，有望用這種方法直接攻克。

聊了一整個(gè)周末，兩位科學(xué)家一拍即合，很快開始了合作。

2001年，他們開發(fā)出了預(yù)想中的分子——其一端是與致病蛋白結(jié)合的小分子，另一端則與E3泛素連接酶結(jié)合的多肽。在實(shí)驗(yàn)條件下，研究人員成功展示了它降解致病蛋白質(zhì)的潛力。

從被嘲“不切實(shí)際”到產(chǎn)業(yè)熱點(diǎn)

起初，這項(xiàng)成果并不被主流科學(xué)界看好，因?yàn)楫?dāng)時(shí)的蛋白降解靶向嵌合體在人體細(xì)胞中活性低，遠(yuǎn)遠(yuǎn)達(dá)不到成藥標(biāo)準(zhǔn)，業(yè)內(nèi)大多數(shù)人認(rèn)為它是一種“有趣但不切實(shí)際”的實(shí)驗(yàn)室工具化合物。根據(jù)《自然》雜志2025年的一篇報(bào)道，有一些科學(xué)家想涉足這一全新的領(lǐng)域，只招來了一些同行的不以為然：“蛋白降解靶向嵌合體？那東西永遠(yuǎn)成不了藥。”

但正所謂“十年窗下無人問，一舉成名天下知”，總有一些不被看好的人和事，會(huì)隨著時(shí)間推移爆發(fā)出驚人的潛力。

這些年，在無人在意的角落，克魯斯教授團(tuán)隊(duì)頂住壓力、一步一個(gè)腳印地解決蛋白降解靶向嵌合體的各種硬傷問題，用克魯斯教授的話說，是在不斷“修修補(bǔ)補(bǔ)”。

2008年，他們用小分子替代原本的多肽配體部分，這樣整個(gè)蛋白降解靶向嵌合體都由小分子模塊組成，能提高細(xì)胞膜穿透能力和分子的成藥性。

2013年，兩篇《科學(xué)》論文證明，“老藥”沙利度胺能清除癌細(xì)胞，竟是不經(jīng)意間利用了靶向蛋白降解機(jī)制。而此前，科學(xué)家一直沒完全弄清楚它的原理。這時(shí)人們才意識(shí)到，整個(gè)方向或許真的可行。這個(gè)好消息讓克魯斯教授團(tuán)隊(duì)振奮不已：這條路還能走，可能走得通！同年，克魯斯教授聯(lián)合創(chuàng)立了專研蛋白降解靶向嵌合體的Arvinas公司。

2015年，多個(gè)研究團(tuán)隊(duì)在細(xì)胞和動(dòng)物模型中實(shí)現(xiàn)了靶蛋白的高效降解，打破了蛋白降解靶向嵌合體“無法成藥”的看法，也為產(chǎn)業(yè)界注入了信心。一大批專注于蛋白質(zhì)降解的新興企業(yè)如雨后春筍般涌現(xiàn)出來。如Nurix、Kymera、C4 和PAQ Therapeutics等新銳公司如今均有多款靶向蛋白降解分子處于臨床研究階段；另一方面，多家大型藥企也在通過與新銳公司達(dá)成合作或啟動(dòng)內(nèi)部研發(fā)項(xiàng)目，布局靶向蛋白降解領(lǐng)域。

與此同時(shí)，在解決了口服療法生物利用度的關(guān)鍵挑戰(zhàn)后，靶向蛋白降解藥物的研發(fā)駛上了快車道，挖掘更多候選蛋白降解靶向嵌合體分子、加快啟動(dòng)臨床前研究就成了重中之重。于是出現(xiàn)了開頭那一幕——Arvinas公司選擇藥明康德作為合作伙伴，藥明康德不負(fù)所托，開啟了長達(dá)10年的合作之旅。

近日FDA批準(zhǔn)了首款蛋白降解靶向嵌合體藥物，此時(shí)距離首篇蛋白降解靶向嵌合體論文發(fā)布已經(jīng)過去了二十幾年。當(dāng)年風(fēng)華正茂的一群科學(xué)家，如今已兩鬢斑白，他們傾注多年心血，逐步解答一道證明題：利用誘導(dǎo)接近機(jī)制來靶向蛋白降解，能成藥，有治病潛力！

圖片來源：123RF

這些研究也讓業(yè)界逐漸意識(shí)到，蛋白降解靶向嵌合體背后的誘導(dǎo)接近機(jī)制，其潛力不止于蛋白降解本身。通過“拉近”不同分子之間的相互作用，研究者有望重新設(shè)計(jì)細(xì)胞內(nèi)的信號(hào)網(wǎng)絡(luò)，并由此催生出更多全新的治療策略。

從蛋白降解靶向嵌合體到更多創(chuàng)新機(jī)制

在蛋白降解靶向嵌合體領(lǐng)域不斷突圍的同時(shí)，克魯斯教授并未停下腳步，又提出了一種全新的誘導(dǎo)接近技術(shù)——調(diào)節(jié)誘導(dǎo)接近靶向嵌合體（Regulated Induced Proximity Targeting Chimeras），并在2019年創(chuàng)辦了專攻這一領(lǐng)域的Halda Therapeutics公司。

調(diào)節(jié)誘導(dǎo)接近靶向嵌合體并不直接誘導(dǎo)降解，而是“一只手抓住”在癌細(xì)胞里高表達(dá)的靶點(diǎn)蛋白，“另一只手抓住”細(xì)胞賴以生存的關(guān)鍵蛋白。它們構(gòu)成的三元復(fù)合體結(jié)構(gòu)非常穩(wěn)定，因此癌細(xì)胞內(nèi)的關(guān)鍵蛋白活性會(huì)大大受阻，整個(gè)細(xì)胞也會(huì)在藥物的影響下逐漸死亡。而健康細(xì)胞則由于缺少癌細(xì)胞里的靶點(diǎn)蛋白，不會(huì)形成復(fù)合體，也就不受影響。

▲調(diào)節(jié)誘導(dǎo)接近靶向嵌合體分子的作用機(jī)制（圖片來源：參考資料[19]）

鑒于之前成功合作的經(jīng)驗(yàn)，在成立之初，Halda繼續(xù)選擇與藥明康德合作，并在關(guān)鍵新藥即將進(jìn)入臨床開發(fā)階段時(shí)進(jìn)一步擴(kuò)大了與藥明康德的合作范疇。

2025年，這家公司公布了其在研藥物HLD-0915的1/2期臨床試驗(yàn)結(jié)果。在研究中，這款靶向雄激素受體的在研療法表現(xiàn)出令人鼓舞的抗腫瘤活性。2025年年底，強(qiáng)生以總額30.5億美元完成了對(duì)Halda Therapeutics的收購。

2024年藥明康德投資者開放日上的報(bào)告指出，這兩個(gè)例子生動(dòng)地說明了藥明康德如何站在產(chǎn)業(yè)創(chuàng)新前沿，通過賦能生物技術(shù)新銳公司，將突破性的科學(xué)研究轉(zhuǎn)化為拯救病患的療法。

Arvinas時(shí)任董事長、總裁兼首席執(zhí)行官John Houston博士也曾在一次公開訪談中感慨道：“如果沒有這種合作關(guān)系，我們就不會(huì)走到今天的位置?！?/p>

近10年來，在“誘導(dǎo)接近”領(lǐng)域，各類創(chuàng)新分子類型也在不斷涌現(xiàn)，呈現(xiàn)出百花齊放的態(tài)勢(shì)。

從機(jī)制上看，這類療法主要分為兩大類：單價(jià)分子膠（molecular glues）與雙功能分子（bifunctional molecules），后者既包括蛋白降解靶向嵌合體與調(diào)節(jié)誘導(dǎo)接近靶向嵌合體分子、化學(xué)誘導(dǎo)二聚體（CIDs）、RNA靶向降解分子這些化學(xué)小分子，也涵蓋雙特異性抗體和納米抗體偶聯(lián)物這些生物大分子。

誘導(dǎo)接近機(jī)制的提出，讓藥物不再只是抑制或激活某個(gè)靶點(diǎn)，而是通過“撮合”兩類生物大分子在細(xì)胞內(nèi)相遇，激活天然信號(hào)通路，改變蛋白功能或水平。由此，研究者能夠通過重塑細(xì)胞內(nèi)蛋白網(wǎng)絡(luò)，影響過去無法觸及的靶點(diǎn)，實(shí)現(xiàn)更廣泛的治療可能。

截至目前，全球共有百余款誘導(dǎo)接近療法正處于積極的臨床研究中，靶點(diǎn)涵蓋AR、BTK、BCL、EGFR、KRAS、CDK、轉(zhuǎn)錄因子IKZF、IRAK等，主要聚焦于腫瘤領(lǐng)域，其次還涉及類風(fēng)濕性關(guān)節(jié)炎、特應(yīng)性皮炎等自身免疫性疾病，痤瘡、脂溢性皮炎、慢性自發(fā)性蕁麻疹等皮膚病，以及慢阻肺、哮喘等呼吸道疾病。其中，多款療法已進(jìn)入3期臨床階段，針對(duì)多種不同的癌癥。隨著研發(fā)進(jìn)程的持續(xù)推進(jìn)，這些新療法未來有望推動(dòng)誘導(dǎo)接近領(lǐng)域邁入新階段，為患者帶來新的治療選擇。

賦能創(chuàng)新，相互成就，攜手共贏

20多年來，以蛋白降解靶向嵌合體與調(diào)節(jié)誘導(dǎo)接近靶向嵌合體為代表的誘導(dǎo)接近療法領(lǐng)域，經(jīng)歷了從不被看好到爭相布局、從“難以成藥”到獲得FDA批準(zhǔn)上市，這種巨大轉(zhuǎn)變，離不開無數(shù)科學(xué)家與產(chǎn)業(yè)界人士的創(chuàng)新與堅(jiān)守。

這個(gè)故事，也是這些年來新藥研發(fā)領(lǐng)域飛速發(fā)展的一個(gè)縮影——曾經(jīng)“不可成藥、難以成藥”的靶點(diǎn)，如今有了成藥的希望，各類新的治療模式也展現(xiàn)出治療復(fù)雜疾病的潛力。

盡管這些科學(xué)創(chuàng)想在轉(zhuǎn)化為現(xiàn)實(shí)療法的道路上，常會(huì)經(jīng)歷各種艱難險(xiǎn)阻，但心懷科學(xué)夢(mèng)想的人，無論是創(chuàng)新者還是賦能者，都堅(jiān)信一件事：在沒有路的地方，就去闖出一條路，逢山開路，遇水搭橋。

20多年來，藥明康德始終致力于幫助各類規(guī)模的創(chuàng)新者降低研發(fā)門檻，賦能全球醫(yī)藥創(chuàng)新。去年行業(yè)媒體STAT的一篇文章中這樣描述藥明康德對(duì)合作伙伴的助力：藥明康德致力于支持全球客戶加速研發(fā)進(jìn)程，從小型和新銳生物技術(shù)公司（biotech）到大型藥企，其CRDMO平臺(tái)能夠“端到端”助力靶向蛋白降解分子從發(fā)現(xiàn)、到開發(fā)，再到生產(chǎn)交付的全過程。憑借全面綜合的能力，藥明康德能將有潛力的創(chuàng)新想法高效、高質(zhì)量地轉(zhuǎn)化為現(xiàn)實(shí)。

得益于獨(dú)特的CRDMO業(yè)務(wù)模式，藥明康德很高興能在相關(guān)療法領(lǐng)域的發(fā)展初期，就為蛋白降解靶向嵌合體和調(diào)節(jié)誘導(dǎo)接近靶向嵌合體類療法提供研發(fā)賦能，并幾乎全程參與產(chǎn)業(yè)轉(zhuǎn)化歷程。

在一路見證合作伙伴再攀高峰的同時(shí)，藥明康德也在不斷前進(jìn)，提升自己的賦能能力。在蛋白降解靶向嵌合體剛剛起步時(shí)，藥明康德前瞻性地布局了相關(guān)能力和技術(shù)，搭建了集發(fā)現(xiàn)、合成、分析純化和測試等能力于一體的賦能平臺(tái)，助力全球合作伙伴高效推進(jìn)藥物從早期發(fā)現(xiàn)到臨床試驗(yàn)階段；伴隨著新型靶向蛋白降解技術(shù)的持續(xù)涌現(xiàn)，藥明康德緊跟科學(xué)前沿，迅速構(gòu)建相關(guān)技術(shù)平臺(tái)，如今能力已涵蓋蛋白降解靶向嵌合體、調(diào)節(jié)誘導(dǎo)接近靶向嵌合體、分子膠、自噬靶向嵌合體、溶酶體靶向嵌合體、去泛素化酶靶向嵌合體、核糖核酸酶靶向嵌合體、磷酸化誘導(dǎo)嵌合小分子以及抗體偶聯(lián)降解劑等主要分子類型。

無論前路是平坦還是崎嶇，藥明康德都將一如既往，懷著“讓天下沒有難做的藥，難治的病”的愿景，助力創(chuàng)新開拓先鋒們奔赴星海征途，守望曙光來臨。

The Molecule No One Had Seen Before

How WuXi AppTec Turns Innovative Ideas into Drug Candidates

More than a decade ago, a research request arrived at WuXi AppTec from a small biotechnology company few people had heard of.

The documents described a molecule unlike anything the team had encountered before, large in molecular weight and structurally unconventional. As scientists reviewed the proposal, it became clear they were looking at a type of molecule rarely seen in drug development at the time. The novelty of the structure immediately stood out.

The molecule would later become associated with a growing new direction in drug discovery:Proteolysis Targeting Chimeras, an emerging therapeutic concept that sought to eliminate disease-causing proteins rather than simply inhibit them.

At the time, however, both the technology and the company behind it, Arvinas, remained largely unknown. The concept of employing induced proximity to draw pathogenic proteins into proximity with intracellular E3 ligases, thereby enabling targeted protein degradation (TPD), was still a developing scientific idea, and few R&D enabling platforms had experience working with molecules of such complexity.

Faced with a project that lay outside conventional boundaries, WuXi AppTec chose to move forward, aiming to support the client’s ambitions and explore new scientific territory alongside them.

That decision marked the beginning of a decade-long collaboration between WuXi AppTec and Arvinas, a partnership that would unfold alongside the gradual rise of targeted protein degradation as an important area of drug discovery.

An Idea Born Over “A Few Beers”

The origins of Proteolysis Targeting Chimeras trace back to 1998, at an academic conference in a seaside resort in Washington State.

There, Prof. Craig Crews of Yale University met Raymond Deshaies, then a professor at the California Institute of Technology. Both scientists were captivated by the same question: could the cell’s own protein disposal machinery be harnessed to treat disease?

Inside every cell there exists a sophisticated quality-control system, a molecular recycling center that identifies and destroys damaged or unnecessary proteins. Scientists had discovered that proteins destined for removal are tagged through ubiquitination, enabling cellular machinery to recognize and eliminate them precisely. The discovery later earned three researchers the 2004 Nobel Prize in Chemistry.

During one discussion, Crews described how small molecules might bring two proteins into proximity. Deshaies, deeply engaged in ubiquitin ligase research, saw an unexpected possibility: if a small molecule could link a target protein to a ubiquitin ligase, could it trigger the protein’s destruction?

The idea immediately resonated. Many diseases are driven by pathogenic proteins long considered difficult or impossible to drug. Instead of blocking their activity, perhaps they could be removed entirely.

The conversation continued throughout the weekend.

“After a few beers,” Crews later recalled, “we started thinking wildly—and realized this could become a transformative therapy.”

Their concept relied on induced proximity: one end of a molecule binds a disease protein, while the other recruits an E3 ubiquitin ligase, bringing the two together so the target protein can be labeled and eliminated by the cell’s recycling machinery.

Compared with traditional inhibitors, which function like keys locking a protein’s active site, the approach offers a different strategy.Roughly 85% of disease-related proteins lack suitable binding pockets, making them difficult to target with conventional drugs.Even successful inhibitors often lose effectiveness due to resistance.

Proteolysis Targeting Chimeras proposed bypassing the need for inhibition altogether by removing the protein itself.

By 2001, the researchers demonstrated experimentally that such targeted degradation was possible.

From Skepticism to Momentum

Early reactions from the scientific community were cautious. Initial Proteolysis Targeting Chimeras showed limited cellular activity and fell short of drug-development expectations. A report published in Nature noted that in the early days, many researchers viewed them as intriguing experimental tools rather than viable therapeutics, and skepticism remained widespread.

Progress, however, continued steadily.

Over the following years, Professor Crews’ team refined the technology through what he later described as continuous “tinkering.” A turning point came in 2008, when the entire molecule had a new design, which is close to its current version, improving permeability and drug-like properties.

Momentum grew further in 2013, when two papers published in Science revealed that the anticancer effects of thalidomide relied on targeted protein degradation mechanisms. The findings suggested that the underlying concept might already have clinical precedent. That same year, Crews co-founded Arvinasto translate the approach into therapeutics.

By 2015, multiple research groups demonstrated efficient protein degradation in cellular and animal models, helping shift industry perception. Interest expanded rapidly, and new companies focused on protein degradation began to emerge. Since then, companies such as Nurix Therapeutics, Kymera Therapeutics, C4 Therapeutics, and PAQ Therapeutics have advanced multiple targeted protein degradation molecules into clinical development. Meanwhile, big pharmaceutical companies are actively building pipelines in this area by collaborating with emerging companies or starting internal development.

After key oral bioavailability challenges were addressed at the same time, development accelerated. Arvinas selected WuXi AppTec as a strategic partner to support expanding discovery and preclinical efforts, initiating a collaboration that would extend over the next decade.

Recently, more than two decades after Proteolysis Targeting Chimeras were first described in the scientific literature, the FDA approved Veppanu (vepdegestrant), marking the first approval of a drug based on this technology.The pioneers in the field now have gray hair at their temples. They have devoted much of their lives to answering a single question: proving that targeted protein degradation through an induced proximity mechanism can be developed into medicines with the potential to treat disease.

These advances have also prompted the scientific community to recognize that the potential of induced proximity extends beyond protein degradation alone. By bringing different molecules into proximity and reshaping interactions within cellular networks, researchers are beginning to design entirely new therapeutic strategies based on this underlying mechanism.

From Proteolysis Targeting Chimeras to More Innovation

As Proteolysis Targeting Chimeras advanced, Professor Crews continued exploring new scientific directions.

In 2019,he introduced Regulated Induced Proximity Targeting Chimeras, a new modality based on the induced proximity concept, and foundedHalda Therapeutics.

Unlike Proteolysis Targeting Chimeras, these molecules do not induce degradation directly. Instead, they form a ternary complex that selectively disrupts survival pathways in cancer cells: one end binds a tumor-specific protein, while the other engages a protein essential for cell survival. The stable complex impedes the function of the essential protein and thus cause selective cancer cell death.

Healthy cells, on the other hand, remain largely unaffected since they don’t have such a high level of tumor-specific proteins.

Building on earlier collaboration experience, Halda partnered with WuXi AppTec from its founding and later expanded the collaboration as clinical development advanced.

In 2025, Halda reported encouraging antitumor activity signals from a Phase 1/2 trial of its androgen receptor–targeting candidate HLD-0915. In late 2025,Johnson & Johnson completed the acquisition of Halda Therapeutics for $3.05 billion.

Together, these developments illustrated how induced proximity strategies were expanding the boundaries of small-molecule therapeutics.

As noted at the WuXi AppTec 2024 Investor Day, these examples show how WuXi AppTec stands at the innovation forefront, and enables new biotech companies to discover and develop lifesaving medicines from breakthrough sciences.

Former Arvinas CEO Dr. John Houston also reflected: “Without this partnership, we would not be where we are today.”

Over the past decade, within the induced proximity field, a wide variety of innovative molecular modalities have continued to emerge, creating a landscape characterized by remarkable diversity.

Mechanistically, these therapies can be broadly divided into two categories: monovalent molecular glues and bifunctional molecules. The latter include small molecules such as Proteolysis Targeting Chimera and Regulated Induced Proximity Targeting Chimera molecules, Chemically Induced Dimerizers, and RNA-targeting degraders, as well as biologics such as bispecific antibodies and nanobody conjugates.

The concept of induced proximity has fundamentally changed how drugs can work.Instead of merely inhibiting or activating a specific target, these therapies function by “bringing together” two biological macromolecules within cells, thereby activating natural signaling pathways and altering protein function or abundance. By reshaping intracellular protein networks in this way, researchers can influence previously inaccessible targets and unlock broader therapeutic possibilities.

To date, more than 100 induced proximity therapies are currently undergoing active clinical investigation worldwide. Their targets include AR, BTK, BCL, EGFR, KRAS, CDK, transcription factors such as IKZF, and IRAK, among others. Most programs focus on oncology, while others extend into autoimmune diseases such as rheumatoid arthritis and atopic dermatitis; dermatological conditions including acne, seborrheic dermatitis, and chronic spontaneous urticaria; as well as respiratory diseases such as chronic obstructive pulmonary disease and asthma. Several candidates have already advanced into Phase 3 clinical trials across multiple cancer indications. As development continues to progress, these emerging therapies are expected to propel the induced proximity field into a new era, offering patients new treatment options.

Enabling Innovation, Growing Together

Over more than two decades, the field of induced proximity therapies, including Proteolysis Targeting Chimeras and Regulated Induced Proximity Targeting Chimeras, has undergone a remarkable transformation. What was once met with skepticism has become a rapidly expanding area of investment and development. The transformation reflects sustained collaboration between academic innovators and industrial partners working to translate discovery into medicine.

An article published in STAT last year described WuXi AppTec’s role this way: WuXi AppTec supports customers from small and emerging biotechs to large pharmas in advancing their pioneering TPD projects across all stages of its CRDMO platform—from discovery to development and delivery. Its comprehensive capabilities enable the company to help transform promising ideas into reality with speed and quality.

As one of the earliest companies enabling both Proteolysis Targeting Chimera and Regulated Induced Proximity Targeting Chimera programs, WuXi AppTec contributed to bridging foundational science and industrial development through its integrated CRDMO model.

Over time, WuXi AppTec expanded its capabilities alongside the growth of the field itself. Early investments established integrated platforms spanning discovery, synthesis, analytical purification, and testing, enabling partners to advance programs efficiently toward clinical development. As new targeted protein degradation modalities emerged, including molecular glues, Autophagy Targeting Chimeras, Lysosome Targeting Chimeras, Deubiquitinase Targeting Chimeras, Ribonuclease Targeting Chimeras, Phosphorylation Inducing Chimeric Small Molecules, and Degrader Antibody Conjugates, the company continued to broaden its technical infrastructure.

Across laboratories worldwide, molecules emerging from these collaborations are steadily moving closer to patients.

The Road Ahead

Scientific progress rarely follows a straight path. It advances through persistence, collaboration, and a willingness to explore unfamiliar ground.

The story of induced proximity drugs such as Proteolysis Targeting Chimeras and Regulated Induced Proximity Targeting Chimeras reflects decades of inquiry driven by a simple belief: when no path exists, one can be created.

Guided by its vision“Every drug can be made, and every disease can be treated,”WuXi AppTec continues to support innovators pursuing the next generation of therapies, helping translate scientific possibility into tangible medical progress.

Somewhere today, another unfamiliar molecule is being examined for the first time.

And another chapter in drug discovery is beginning.

參考資料:

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[9]攻克“不可成藥”：楊青博士談創(chuàng)新療法的突破與合作 | Bilingual. Retrieved Feb 13, 2026 from https://mp.weixin.qq.com/s/01fOJJc6x7OOjY4oGPm66w

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[17]Avram Hershko Facts. Retrieved Feb 13, 2026 from https://www.nobelprize.org/prizes/chemistry/2004/hershko/facts/

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[19]Raina et al., (2023). Regulated Induced Proximity Targeting Chimeras (RIPTACs): a Novel Heterobifunctional Small Molecule Therapeutic Strategy for Killing Cancer Cells Selectively. bioRxiv, doi: https://doi.org/10.1101/2023.01.01.522436

免責(zé)聲明：本文僅作信息交流之目的，文中觀點(diǎn)不代表藥明康德立場，亦不代表藥明康德支持或反對(duì)文中觀點(diǎn)。本文也不是治療方案推薦。如需獲得治療方案指導(dǎo)，請(qǐng)前往正規(guī)醫(yī)院就診。

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