NPASS Compound

Natural Product: NPC156797

Natural Product ID	NPC156797
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	6Alpha-Chloro-5Beta-Hydroxywithaferin A
IUPAC Name	(2R)-2-[(1S)-1-[(4S,5R,6S,8S,9S,10R,13S,14S,17R)-6-chloro-4,5-dihydroxy-10,13-dimethyl-1-oxo-6,7,8,9,11,12,14,15,16,17-decahydro-4H-cyclopenta[a]phenanthren-17-yl]ethyl]-5-(hydroxymethyl)-4-methyl-2,3-dihydropyran-6-one
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL2047417
PubChem CID	70686220
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0000258] Steroids and steroid derivatives [CHEMONTID:0001125] Steroid lactones [CHEMONTID:0001560] Withanolides and derivatives

The Chemical Classification was calculated by Classyfire, a software for chemical taxonomy calculation. Reference: DOI:10.1186/s13321-016-0174-y.

Chemical Representations

RDKit 3D 74 78 0 0 0 0 0 0 0 0999 V2000 6.8866 -1.5458 -0.9246 C 0 0 0 0 0 0 0 0 0 0 0 0 5.9336 -0.5330 -0.4191 C 0 0 0 0 0 0 0 0 0 0 0 0 6.3471 0.6597 -0.0717 C 0 0 0 0 0 0 0 0 0 0 0 0 7.8083 1.0177 -0.1877 C 0 0 0 0 0 0 0 0 0 0 0 0 7.9898 2.0813 -1.0355 O 0 0 0 0 0 0 0 0 0 0 0 0 5.4013 1.6425 0.4646 C 0 0 0 0 0 0 0 0 0 0 0 0 5.8133 2.8062 0.7955 O 0 0 0 0 0 0 0 0 0 0 0 0 4.0785 1.2371 0.5816 O 0 0 0 0 0 0 0 0 0 0 0 0 3.8727 -0.1540 0.7535 C 0 0 2 0 0 0 0 0 0 0 0 0 4.4726 -0.9013 -0.3509 C 0 0 0 0 0 0 0 0 0 0 0 0 2.5111 -0.4941 1.2519 C 0 0 1 0 0 0 0 0 0 0 0 0 2.4275 0.2033 2.6091 C 0 0 0 0 0 0 0 0 0 0 0 0 1.4452 -0.1493 0.3274 C 0 0 1 0 0 0 0 0 0 0 0 0 1.5809 -0.8894 -0.9750 C 0 0 0 0 0 0 0 0 0 0 0 0 0.1474 -1.3268 -1.3587 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.6313 -0.3208 -0.6536 C 0 0 1 0 0 0 0 0 0 0 0 0 -2.0685 -0.5532 -0.4089 C 0 0 2 0 0 0 0 0 0 0 0 0 -2.8653 -1.0344 -1.5773 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.2520 -1.3659 -1.0636 C 0 0 1 0 0 0 0 0 0 0 0 0 -4.7118 -0.4743 0.0369 C 0 0 2 0 0 0 0 0 0 0 0 0 -6.2178 -0.3274 -0.0308 C 0 0 2 0 0 0 0 0 0 0 0 0 -6.6970 0.4438 -1.1715 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.9529 1.3395 -1.7793 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.6100 1.5459 -1.2737 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.8486 2.3046 -1.9191 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.0718 0.9190 -0.0401 C 0 0 1 0 0 0 0 0 0 0 0 0 -4.5833 1.7492 1.1198 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.5827 0.8320 -0.0569 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.9036 1.3323 1.1652 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.5615 0.8521 1.4799 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0236 -0.2891 0.7300 C 0 0 2 0 0 0 0 0 0 0 0 0 -0.1968 -1.5927 1.4519 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.7110 0.1502 1.2039 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.4529 -1.0346 1.3115 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.4266 -1.5214 -2.3878 Cl 0 0 0 0 0 0 0 0 0 0 0 0 7.5603 -1.9362 -0.1388 H 0 0 0 0 0 0 0 0 0 0 0 0 6.3428 -2.4365 -1.3382 H 0 0 0 0 0 0 0 0 0 0 0 0 7.5514 -1.1363 -1.7328 H 0 0 0 0 0 0 0 0 0 0 0 0 8.1071 1.3682 0.8432 H 0 0 0 0 0 0 0 0 0 0 0 0 8.4147 0.1360 -0.3924 H 0 0 0 0 0 0 0 0 0 0 0 0 7.1529 2.4995 -1.3413 H 0 0 0 0 0 0 0 0 0 0 0 0 4.5532 -0.3936 1.6646 H 0 0 0 0 0 0 0 0 0 0 0 0 4.3905 -2.0111 -0.2660 H 0 0 0 0 0 0 0 0 0 0 0 0 4.0988 -0.5416 -1.3488 H 0 0 0 0 0 0 0 0 0 0 0 0 2.5311 -1.5835 1.4766 H 0 0 0 0 0 0 0 0 0 0 0 0 2.2982 1.3019 2.4977 H 0 0 0 0 0 0 0 0 0 0 0 0 1.6419 -0.1521 3.2578 H 0 0 0 0 0 0 0 0 0 0 0 0 3.3949 0.0822 3.1548 H 0 0 0 0 0 0 0 0 0 0 0 0 1.5696 0.9587 0.0616 H 0 0 0 0 0 0 0 0 0 0 0 0 1.8545 -0.2101 -1.8184 H 0 0 0 0 0 0 0 0 0 0 0 0 2.1517 -1.8181 -0.9266 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.0148 -1.1899 -2.4699 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.0195 -2.3777 -1.1744 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.4039 0.6854 -1.0968 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.2770 -1.2010 0.4456 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.9901 -0.2679 -2.3649 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.4505 -1.9494 -2.0243 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.1588 -2.4026 -0.6225 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.6215 -1.3807 -0.0957 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.7178 0.2598 -1.5252 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.3753 1.8733 -2.6187 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.9246 2.6394 1.1951 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.5929 2.1681 0.8332 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.6728 1.1752 2.0448 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.2317 1.4814 -0.9154 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.8964 2.4629 1.0889 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.6342 1.1580 2.0151 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.5392 0.5699 2.5766 H 0 0 0 0 0 0 0 0 0 0 0 0 0.1901 1.6965 1.4241 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.4667 -2.4429 0.7870 H 0 0 0 0 0 0 0 0 0 0 0 0 0.6561 -1.9456 2.0433 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.1250 -1.4925 2.1016 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.5669 0.5935 1.0087 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.1741 -0.8489 1.9380 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 2 0 3 4 1 0 4 5 1 0 3 6 1 0 6 7 2 0 6 8 1 0 8 9 1 0 9 10 1 0 9 11 1 0 11 12 1 0 11 13 1 0 13 14 1 0 14 15 1 0 15 16 1 0 16 17 1 0 17 18 1 0 18 19 1 0 19 20 1 0 20 21 1 0 21 22 1 0 22 23 2 0 23 24 1 0 24 25 2 0 24 26 1 0 26 27 1 1 26 28 1 0 28 29 1 0 29 30 1 0 30 31 1 0 31 32 1 1 21 33 1 0 20 34 1 1 19 35 1 0 10 2 1 0 31 13 1 0 31 16 1 0 28 17 1 0 26 20 1 0 1 36 1 0 1 37 1 0 1 38 1 0 4 39 1 0 4 40 1 0 5 41 1 0 9 42 1 1 10 43 1 0 10 44 1 0 11 45 1 1 12 46 1 0 12 47 1 0 12 48 1 0 13 49 1 6 14 50 1 0 14 51 1 0 15 52 1 0 15 53 1 0 16 54 1 6 17 55 1 1 18 56 1 0 18 57 1 0 19 58 1 1 21 59 1 6 22 60 1 0 23 61 1 0 27 62 1 0 27 63 1 0 27 64 1 0 28 65 1 6 29 66 1 0 29 67 1 0 30 68 1 0 30 69 1 0 32 70 1 0 32 71 1 0 32 72 1 0 33 73 1 0 34 74 1 0 M END

Standard InCHIKey	YCFROFMCBMCGDC-PNJOURQRSA-N
Standard InCHI	InChI=1S/C28H39ClO6/c1-14-11-21(35-25(33)17(14)13-30)15(2)18-5-6-19-16-12-22(29)28(34)24(32)8-7-23(31)27(28,4)20(16)9-10-26(18,19)3/h7-8,15-16,18-22,24,30,32,34H,5-6,9-13H2,1-4H3/t15-,16-,18+,19-,20-,21+,22-,24-,26+,27-,28-/m0/s1
SMILES	CC1=C(CO)C(=O)O[C@H](C1)[C@@H](C)[C@H]1CC[C@H]2[C@@H]3C[C@@H]([C@@]4([C@H](C=CC(=O)[C@]4(C)[C@H]3CC[C@]12C)O)O)Cl

Calculated Properties

Physi-Chem Properties

Molecular Weight:	506.24	Volume:	507.468 ? Van der Waals volume.
Dense:	0.998	LogP:	3.15 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.453 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.487 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	3.0	Rigid Bonds:	28.0
TPSA:	104.06 ? Topological Polar Surface Area.	H-Bond Acceptor:	6.0
H-Bond Donor:	3.0	Rings:	5.0
Heavy Atoms:	7.0

MedChem Properties

QED Drug-Likeness Score:	0.399	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	5.42	Fsp³:	0.786
MCE-18:	95.04 ? MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.	Lipinski Rule-of-5:	Rejected
Pfizer Rule:	Rejected	GSK Rule:	Accepted
Golden Triangle Rule:	Accepted	BMS Rule:	1
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.441	Fluc inhibitor:	0.104 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.003 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.0 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.416	Promiscuous compounds:	0.639

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.544	MDCK Permeability:	-5.09
Pgp-inhibitor:	0.003	Pgp-substrate:	0.002
PAMPA:	0.25 ? The experimental data for Peff was logarithmically transformed (logPeff). Molecules with log Peff values below 2.0 were classified as low-permeability (Category 0), while those with log Peff values exceeding 2.5 were classified as high-permeability (Category 1).	Human Intestinal Absorption (HIA):	0.001
20% Bioavailability (F20%):	0.006	30% Bioavailability (F30%):	0.449
50% Bioavailability (F50%):	0.979

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.024	MRP1:	0.131
Plasma Protein Binding (PPB):	88.988%	Volume Distribution (VD):	-0.09
Fu:	8.483% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	1.0
OATP1B3 inhibitor:	1.0	BCRP inhibitor:	0.006
BSEP inhibitor:	0.994

ADMET: Metabolism

CYP1A2-inhibitor:	0.001	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.362	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.054	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.0
CYP3A4-inhibitor:	0.046	CYP3A4-substrate:	0.996
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.993
HLM stability:	0.936 ? Human liver microsomal (HLM) stability. Category 0: stable+ (HLM > 30 min); Category 1: unstable- (HLM ≤ 30 min). The output value is the probability of human liver microsomal instability, where a value closer to 1 indicates a higher likelihood of instability.

ADMET: Excretion

Clearance (CL):

6.94

Half-life (T1/2):

1.29

ADMET: Toxicity

hERG Blockers:	0.022	hERG Blockers (10um):	0.165
Human Hepatotoxicity (H-HT):	0.552	Drug-induced Liver Injury (DILI):	0.157
AMES Toxicity:	0.524	Rat Oral Acute Toxicity:	0.155
Maximum Recommended Daily Dose:	0.642	Skin Sensitization:	0.999
Carcinogencity:	0.961	Eye Corrosion:	0.05
Eye Irritation:	0.9	Respiratory Toxicity:	0.941
Drug-induced Neurotoxicity:	0.063	Ototoxicity:	0.711
Hematotoxicity:	0.648	Drug-induced Nephrotoxicity:	0.931
Genotoxicity:	0.898	RPMI-8226 Immunitoxicity:	0.082
A549 Cytotoxicity:	0.11	Hek293 Cytotoxicity:	0.575
BCF:	1.029 ? Bioconcentration factors are used for considering secondary poisoning potential and assessing risks to human health via the food chain. The unit is -log10[(mg/L)/(1000*MW)].	IGC50:	3.745 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.539 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.798 ? 96 hour fathead minnow LC50. The unit of LC50FM is -log10[(mg/L)/(1000*MW)].

Species Source

Organism ID	Organism Name	Taxonomy Level	Family	SuperKingdom	Isolation Part	Collection Location	Collection Time	Reference
NPO20281	Withania aristata	Species	Solanaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[22705001]
NPO20281	Withania aristata	Species	Solanaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO20281	Withania aristata	Species	Solanaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]

Note for Reference:
In addition to directly collecting NP source organism data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated them from below databases:
☉ UNPD: Universal Natural Products Database [PMID: 23638153].
☉ StreptomeDB: a database of streptomycetes natural products [PMID: 33051671].
☉ TM-MC: a database of medicinal materials and chemical compounds in Northeast Asian traditional medicine [PMID: 26156871].
☉ TCM@Taiwan: a Traditional Chinese Medicine database [PMID: 21253603].
☉ TCMID: a Traditional Chinese Medicine database [PMID: 29106634].
☉ TCMSP: The traditional Chinese medicine systems pharmacology database and analysis platform [PMID: 24735618].
☉ HerDing: a herb recommendation system to treat diseases using genes and chemicals [PMID: 26980517].
☉ MetaboLights: a metabolomics database [PMID: 27010336].
☉ FooDB: a database of constituents, chemistry and biology of food species [www.foodb.ca].

NP Quantity Composition/Concentration

Organism ID	Organism Name	Organism Material Preparation	Organism Part	NP Quantity (Standard)	NP Quantity (Minimum)	NP Quantity (Maximum)	Quantity Unit	Reference

Note for Reference:
In addition to directly collecting NP quantitative data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated NP quantitative records for specific NP domains (e.g., NPS from foods or herbs) from domain-specific databases. These databases include:
☉ DUKE: Dr. Duke's Phytochemical and Ethnobotanical Databases.
☉ PHENOL EXPLORER: is the first comprehensive database on polyphenol content in foods [PMID: 24103452], its homepage can be accessed at here.
☉ FooDB: a database of constituents, chemistry and biology of food species [www.foodb.ca].

Biological Activity

Activity Type	# Activity
IC50	16
Ratio IC50	1

Activity Type	# Activity
Cell line	17

Molecular-level activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference

In vitro activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT165	Cell line	HeLa	Homo sapiens	IC50	=	13400.0	nM	PMID[1336040]
NPT81	Cell line	A549	Homo sapiens	IC50	=	14700.0	nM	PMID[15844960]
NPT165	Cell line	HeLa	Homo sapiens	IC50	=	12100.0	nM	PubChem BioAssay data set
NPT81	Cell line	A549	Homo sapiens	IC50	=	8600.0	nM	PMID[22928967]
NPT83	Cell line	MCF7	Homo sapiens	IC50	=	7500.0	nM	PMID[24571273]
NPT83	Cell line	MCF7	Homo sapiens	IC50	=	1300.0	nM	PubChem BioAssay data set
NPT189	Cell line	Vero	Chlorocebus aethiops	IC50	=	14800.0	nM	DrugMatrix in vitro pharmacology data
NPT189	Cell line	Vero	Chlorocebus aethiops	IC50	=	7800.0	nM	PMID[19105653]
NPT189	Cell line	Vero	Chlorocebus aethiops	Ratio IC50	=	2.0	n.a.	PMID[18077363]
NPT165	Cell line	HeLa	Homo sapiens	IC50	=	17500.0	nM	PMID[28923386]
NPT81	Cell line	A549	Homo sapiens	IC50	=	16100.0	nM	PMID[28923386]
NPT83	Cell line	MCF7	Homo sapiens	IC50	=	7900.0	nM	PMID[28923386]

In vivo activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference

Experimental ADME

Experiment Model	Experiment Tissue	ADME Type	ADME Relation	ADME Value	ADME Unit	Reference

Experimental Toxicity

Quantitative toxicity

Experiment Model	Experiment Organism	Toxicity Type	Toxicity Relation	Toxicity Value	Toxicity Unit	Reference

Common Abbreviations:
LC: Lethal Concentration; LD: Lethal Dose; LT:Lethal Time; NOAEL: No-observed-adverse-effect Level; BMDL: Benchmark Dose Lower Confidence Limit; BMD: Benchmark Dose; BMC:Benchmark Concentration; LOAEL: Lowest Observed Adverse Effect Level; RfD:Reference Dose; RfC:Reference Concentration; MRL: Minimal Risk Level; MEG: Maximum Exposure Guideline; PAC: Protective Action Criteria

Categorical toxicity labels

Hepatotoxicity	Carcinogenicity	Mutagenicity	Cardiotoxicity	Respiratory Toxicity	Eye Irritation	Endocrine Disruption

Note for Reference:
In addition to directly collecting NP quantitative data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated NP toxicity records from domain-specific databases. These databases include:
☉ ToxValDB: a curated database that compiles quantitative toxicity values for chemicals from diverse public sources to support toxicological research and risk assessment.
☉ TOXRIC: a comprehensive, free-to-access, online database providing toxicological/feature data. The toxicity labels are retrieved from this database. [PMID: 36400569]

Chemically structural similarity

Similar Active Natural Products in NPASS

Top-200 similar NPs were calculated against the active-NP-set (includes approximately 50,000 NPs with experimentally-derived bioactivity available in NPASS)

Similarity is measured using the Tanimoto coefficient (Tc) , which compares the binary fingerprints of two molecules. Tc is calculated as the intersection divided by the union of '1' bits in the fingerprints, ranging from 0 to 1, with 1 indicating highest similarity.

● The left chart: Distribution of similarity level between NPC156797 and all remaining natural products in the NPASS database.
● The right table: Most similar natural products (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	17036
0.1-0.2	27734
0.2-0.3	4924
0.3-0.4	119
0.4-0.5	26
0.5-0.6	16
0.6-0.7	2
0.7-0.8	0
0.8-0.85	0
0.85-0.9	0
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.7	Intermediate Similarity	NPC67259
0.6806	Remote Similarity	NPC250312
0.6438	Remote Similarity	NPC147912
0.5867	Remote Similarity	NPC91034
0.5733	Remote Similarity	NPC69291
0.5658	Remote Similarity	NPC474315
0.5641	Remote Similarity	NPC709
0.5641	Remote Similarity	NPC140055
0.5641	Remote Similarity	NPC167606
0.56	Remote Similarity	NPC220155
0.5584	Remote Similarity	NPC55296
0.5443	Remote Similarity	NPC230513
0.5385	Remote Similarity	NPC243065
0.525	Remote Similarity	NPC122056
0.525	Remote Similarity	NPC470265
0.5238	Remote Similarity	NPC473396
0.5185	Remote Similarity	NPC287903
0.5128	Remote Similarity	NPC285956
0.5119	Remote Similarity	NPC473233

Similar Clinical/Approved Drugs

Similarity level is defined by Tanimoto coefficient (Tc) between two molecules.

● The left chart: Distribution of similarity level between NPC156797 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	6077
0.1-0.2	2830
0.2-0.3	242
0.3-0.4	0
0.4-0.5	0
0.5-0.6	1
0.6-0.7	0
0.7-0.8	0
0.8-0.85	0
0.85-0.9	0
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Drug ID	Developmental Stage
0.5641	Remote Similarity	NPD7115	Discovery

Bioactivity similarity

Similar Natural Products in NPASS

Similarity level is defined by Bioactivity similarity was calculated based on bioactivity descriptors of compounds. The bioactivity descriptors were calculated by a recently developed AI algorithm Chemical Checker (CC) [Nature Biotechnology, 38:1087–1096, 2020; Nature Communications, 12:3932, 2021], which evaluated bioactivity similarities at five levels:
☉ A: chemistry similarity;
☉ B: biological targets similarity;
☉ C: networks similarity;
☉ D: cell-based bioactivity similarity;
☉ E: similarity based on clinical data.
Those 5 categories of CC bioactivity descriptors were calculated and then subjected to manifold projection using UMAP algorithm, to project all NPs on a 2-Dimensional space. The current NP was highlighted with a small circle in the 2-D map. Below figures: left-to-right, A-to-E.

A: chemistry similarity

B: biological targets similarity

C: networks similarity

D: cell-based bioactivity similarity

E: similarity based on clinical data