NPASS Compound

Natural Product: NPC5767

Natural Product ID	NPC5767
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Rel-3Alpha,28-Dihydroxy-30-Norlupan-20-One
IUPAC Name	1-[(1R,3aS,5aR,5bR,7aR,9R,11aR,11bR,13aR,13bS)-9-hydroxy-3a-(hydroxymethyl)-5a,5b,8,8,11a-pentamethyl-1,2,3,4,5,6,7,7a,9,10,11,11b,12,13,13a,13b-hexadecahydrocyclopenta[a]chrysen-1-yl]ethanone
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL3109395
PubChem CID	76317491
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0000258] Steroids and steroid derivatives [CHEMONTID:0001295] Hydroxysteroids [CHEMONTID:0004159] 18-hydroxysteroids

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 80 84 0 0 0 0 0 0 0 0999 V2000 -4.8413 0.3401 2.8935 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.9976 -0.2466 1.9108 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.7791 0.7765 0.8508 C 0 0 2 0 0 0 0 0 0 0 0 0 -5.1432 1.1376 0.3003 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.4914 -0.1597 -0.4108 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.1665 -0.6709 -0.9652 C 0 0 2 0 0 0 0 0 0 0 0 0 -3.1340 0.2361 -0.4198 C 0 0 2 0 0 0 0 0 0 0 0 0 -1.8389 -0.3753 0.0007 C 0 0 2 0 0 0 0 0 0 0 0 0 -0.9241 0.8009 0.3427 C 0 0 2 0 0 0 0 0 0 0 0 0 -1.5116 1.6973 1.3900 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.9707 1.9455 1.2757 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.7983 1.6268 -0.9199 C 0 0 0 0 0 0 0 0 0 0 0 0 0.3980 0.2149 0.7817 C 0 0 2 0 0 0 0 0 0 0 0 0 0.1997 -0.6832 1.9641 C 0 0 0 0 0 0 0 0 0 0 0 0 1.2448 1.3685 1.2656 C 0 0 0 0 0 0 0 0 0 0 0 0 2.6964 1.0106 1.4469 C 0 0 0 0 0 0 0 0 0 0 0 0 3.1888 0.4423 0.1497 C 0 0 2 0 0 0 0 0 0 0 0 0 2.4692 -0.8098 -0.2635 C 0 0 2 0 0 0 0 0 0 0 0 0 1.0185 -0.4990 -0.3962 C 0 0 1 0 0 0 0 0 0 0 0 0 0.1710 -1.6736 -0.7813 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.2536 -1.2504 -1.0512 C 0 0 0 0 0 0 0 0 0 0 0 0 2.7759 -2.0072 0.5668 C 0 0 0 0 0 0 0 0 0 0 0 0 2.9854 -1.1209 -1.6774 C 0 0 0 0 0 0 0 0 0 0 0 0 4.4760 -1.3107 -1.7099 C 0 0 0 0 0 0 0 0 0 0 0 0 5.2750 -0.2451 -1.0713 C 0 0 2 0 0 0 0 0 0 0 0 0 4.6728 0.3633 0.1626 C 0 0 0 0 0 0 0 0 0 0 0 0 5.2675 -0.2608 1.3851 C 0 0 0 0 0 0 0 0 0 0 0 0 5.1588 1.8278 0.1558 C 0 0 0 0 0 0 0 0 0 0 0 0 5.6088 0.7380 -2.0326 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.2914 -0.5693 -2.4418 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.5931 0.1492 -3.1179 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.3268 -1.3927 -3.1171 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.5746 -0.2452 3.1419 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.0854 -0.5444 2.4774 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.5280 -1.1445 1.5553 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.0640 1.9836 -0.3792 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.8655 1.3325 1.1208 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.9939 -0.8875 0.2200 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.2040 0.1336 -1.2175 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.0164 -1.7423 -0.7283 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.9913 1.1190 -1.0910 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.0218 -1.0143 0.8766 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.2750 1.4403 2.4273 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.0100 2.7034 1.2353 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.3668 2.3171 2.2383 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.1517 2.7738 0.5338 H 0 0 0 0 0 0 0 0 0 0 0 0 0.1815 2.0937 -1.0670 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.5156 2.5012 -0.8700 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.0583 1.1062 -1.8375 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.7246 -0.5001 2.5469 H 0 0 0 0 0 0 0 0 0 0 0 0 1.0072 -0.5255 2.7447 H 0 0 0 0 0 0 0 0 0 0 0 0 0.2103 -1.7596 1.7505 H 0 0 0 0 0 0 0 0 0 0 0 0 0.8605 1.6338 2.2918 H 0 0 0 0 0 0 0 0 0 0 0 0 1.1869 2.2772 0.6784 H 0 0 0 0 0 0 0 0 0 0 0 0 2.7873 0.3576 2.3071 H 0 0 0 0 0 0 0 0 0 0 0 0 3.2431 1.9559 1.6293 H 0 0 0 0 0 0 0 0 0 0 0 0 2.9193 1.2119 -0.6383 H 0 0 0 0 0 0 0 0 0 0 0 0 0.9378 0.2216 -1.2658 H 0 0 0 0 0 0 0 0 0 0 0 0 0.1938 -2.5301 -0.1158 H 0 0 0 0 0 0 0 0 0 0 0 0 0.5463 -2.0632 -1.7753 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.8557 -2.2088 -1.0440 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.3371 -0.8795 -2.0908 H 0 0 0 0 0 0 0 0 0 0 0 0 2.2786 -2.8817 0.0961 H 0 0 0 0 0 0 0 0 0 0 0 0 2.6005 -1.9214 1.6351 H 0 0 0 0 0 0 0 0 0 0 0 0 3.8789 -2.2149 0.4501 H 0 0 0 0 0 0 0 0 0 0 0 0 2.7354 -0.2756 -2.3535 H 0 0 0 0 0 0 0 0 0 0 0 0 2.5528 -2.0751 -2.0599 H 0 0 0 0 0 0 0 0 0 0 0 0 4.7444 -1.3199 -2.8092 H 0 0 0 0 0 0 0 0 0 0 0 0 4.7860 -2.3423 -1.3682 H 0 0 0 0 0 0 0 0 0 0 0 0 6.2638 -0.6952 -0.7753 H 0 0 0 0 0 0 0 0 0 0 0 0 4.5609 -0.6309 2.1188 H 0 0 0 0 0 0 0 0 0 0 0 0 5.9734 0.4164 1.9365 H 0 0 0 0 0 0 0 0 0 0 0 0 5.9217 -1.1320 1.0849 H 0 0 0 0 0 0 0 0 0 0 0 0 6.2032 1.8214 -0.2253 H 0 0 0 0 0 0 0 0 0 0 0 0 5.2151 2.2277 1.1867 H 0 0 0 0 0 0 0 0 0 0 0 0 4.5552 2.4429 -0.5281 H 0 0 0 0 0 0 0 0 0 0 0 0 6.5539 0.9538 -2.0379 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.1308 -1.5160 -4.1975 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.3362 -0.9625 -2.9355 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.3359 -2.4123 -2.6798 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 3 2 1 1 3 4 1 0 4 5 1 0 5 6 1 0 6 7 1 0 7 8 1 0 8 9 1 0 9 10 1 0 10 11 1 0 9 12 1 6 9 13 1 0 13 14 1 1 13 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 18 22 1 1 18 23 1 0 23 24 1 0 24 25 1 0 25 26 1 0 26 27 1 0 26 28 1 0 25 29 1 0 6 30 1 0 30 31 2 0 30 32 1 0 11 3 1 0 19 13 1 0 7 3 1 0 21 8 1 0 26 17 1 0 1 33 1 0 2 34 1 0 2 35 1 0 4 36 1 0 4 37 1 0 5 38 1 0 5 39 1 0 6 40 1 6 7 41 1 6 8 42 1 1 10 43 1 0 10 44 1 0 11 45 1 0 11 46 1 0 12 47 1 0 12 48 1 0 12 49 1 0 14 50 1 0 14 51 1 0 14 52 1 0 15 53 1 0 15 54 1 0 16 55 1 0 16 56 1 0 17 57 1 6 19 58 1 6 20 59 1 0 20 60 1 0 21 61 1 0 21 62 1 0 22 63 1 0 22 64 1 0 22 65 1 0 23 66 1 0 23 67 1 0 24 68 1 0 24 69 1 0 25 70 1 1 27 71 1 0 27 72 1 0 27 73 1 0 28 74 1 0 28 75 1 0 28 76 1 0 29 77 1 0 32 78 1 0 32 79 1 0 32 80 1 0 M END

Standard InCHIKey	BSALBDFYJLSIOZ-AJVVGMEXSA-N
Standard InCHI	InChI=1S/C29H48O3/c1-18(31)19-9-14-29(17-30)16-15-27(5)20(24(19)29)7-8-22-26(4)12-11-23(32)25(2,3)21(26)10-13-28(22,27)6/h19-24,30,32H,7-17H2,1-6H3/t19-,20+,21-,22+,23+,24+,26-,27+,28+,29+/m0/s1
SMILES	OC[C@@]12CC[C@H]([C@@H]2[C@@H]2[C@](CC1)(C)[C@]1(C)CC[C@@H]3[C@]([C@H]1CC2)(C)CC[C@H](C3(C)C)O)C(=O)C

Calculated Properties

Physi-Chem Properties

Molecular Weight:	444.36	Volume:	491.092 ? Van der Waals volume.
Dense:	0.905	LogP:	4.128 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.951 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.517 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	2.0	Rigid Bonds:	26.0
TPSA:	57.53 ? Topological Polar Surface Area.	H-Bond Acceptor:	3.0
H-Bond Donor:	2.0	Rings:	5.0
Heavy Atoms:	3.0

MedChem Properties

QED Drug-Likeness Score:	0.548	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.745	Fsp³:	0.966
MCE-18:	101.263 ? MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.	Lipinski Rule-of-5:	Rejected
Pfizer Rule:	Accepted	GSK Rule:	Accepted
Golden Triangle Rule:	Rejected	BMS Rule:	0
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.852	Fluc inhibitor:	0.006 ? 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:	0.381	Promiscuous compounds:	0.438

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.458	MDCK Permeability:	-5.002
Pgp-inhibitor:	0.223	Pgp-substrate:	0.573
PAMPA:	0.52 ? 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):	0.0
20% Bioavailability (F20%):	0.146	30% Bioavailability (F30%):	0.245
50% Bioavailability (F50%):	0.968

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.73	MRP1:	0.983
Plasma Protein Binding (PPB):	89.966%	Volume Distribution (VD):	-0.121
Fu:	10.68% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.995
OATP1B3 inhibitor:	0.669	BCRP inhibitor:	0.114
BSEP inhibitor:	0.949

ADMET: Metabolism

CYP1A2-inhibitor:	0.002	CYP1A2-substrate:	0.002
CYP2C19-inhibitor:	0.969	CYP2C19-substrate:	0.119
CYP2C9-inhibitor:	0.001	CYP2C9-substrate:	0.038
CYP2D6-inhibitor:	0.865	CYP2D6-substrate:	0.007
CYP3A4-inhibitor:	0.937	CYP3A4-substrate:	0.018
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.902
HLM stability:	0.827 ? 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):

11.195

Half-life (T1/2):

1.069

ADMET: Toxicity

hERG Blockers:	0.061	hERG Blockers (10um):	0.16
Human Hepatotoxicity (H-HT):	0.572	Drug-induced Liver Injury (DILI):	0.187
AMES Toxicity:	0.425	Rat Oral Acute Toxicity:	0.142
Maximum Recommended Daily Dose:	0.549	Skin Sensitization:	0.902
Carcinogencity:	0.9	Eye Corrosion:	0.028
Eye Irritation:	0.664	Respiratory Toxicity:	0.856
Drug-induced Neurotoxicity:	0.04	Ototoxicity:	0.507
Hematotoxicity:	0.514	Drug-induced Nephrotoxicity:	0.7
Genotoxicity:	0.47	RPMI-8226 Immunitoxicity:	0.064
A549 Cytotoxicity:	0.099	Hek293 Cytotoxicity:	0.278
BCF:	1.585 ? 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:	3.682 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.129 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.459 ? 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
NPO33010	euonymus carnosus	Species	Celastraceae	Eukaryota	Plant	n.a.	n.a.	PMID[24467317]

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	6

Activity Type	# Activity
Cell line	2
Non-molecular	4

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
NPT179	Cell line	A2780	Homo sapiens	IC50	>	10000.0	nM	PubChem BioAssay data set
NPT81	Cell line	A549	Homo sapiens	IC50	>	10000.0	nM	PMID[14738384]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	IC50	>	10000.0	nM	PMID[24467317]

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 NPC5767 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	21499
0.1-0.2	24238
0.2-0.3	3508
0.3-0.4	487
0.4-0.5	75
0.5-0.6	36
0.6-0.7	6
0.7-0.8	0
0.8-0.85	0
0.85-0.9	0
0.9-0.95	0
0.95-1	1

Similarity Score	Similarity Level	Natural Product ID
1.0	High Similarity	NPC475742
0.7843	Intermediate Similarity	NPC97534
0.7843	Intermediate Similarity	NPC195155
0.7347	Intermediate Similarity	NPC232112
0.7222	Intermediate Similarity	NPC231256
0.7222	Intermediate Similarity	NPC178383
0.6964	Remote Similarity	NPC119355
0.678	Remote Similarity	NPC289486
0.661	Remote Similarity	NPC61107
0.614	Remote Similarity	NPC78067
0.614	Remote Similarity	NPC278091
0.6	Remote Similarity	NPC142712
0.5893	Remote Similarity	NPC480925
0.5893	Remote Similarity	NPC48079
0.5833	Remote Similarity	NPC74595
0.5833	Remote Similarity	NPC264665
0.5833	Remote Similarity	NPC269396
0.5789	Remote Similarity	NPC192638
0.5789	Remote Similarity	NPC25511
0.5789	Remote Similarity	NPC600137
0.5763	Remote Similarity	NPC248830
0.5763	Remote Similarity	NPC212241
0.5714	Remote Similarity	NPC30583
0.5645	Remote Similarity	NPC12774
0.5625	Remote Similarity	NPC483720
0.5593	Remote Similarity	NPC144075
0.5593	Remote Similarity	NPC301226
0.5484	Remote Similarity	NPC298168
0.5484	Remote Similarity	NPC143133
0.541	Remote Similarity	NPC201725
0.541	Remote Similarity	NPC93662
0.5385	Remote Similarity	NPC481321
0.5385	Remote Similarity	NPC607755
0.5323	Remote Similarity	NPC246956
0.5323	Remote Similarity	NPC201459
0.5323	Remote Similarity	NPC86305
0.5323	Remote Similarity	NPC212879
0.5312	Remote Similarity	NPC477578
0.5312	Remote Similarity	NPC477577
0.5246	Remote Similarity	NPC58631
0.5238	Remote Similarity	NPC126993
0.5161	Remote Similarity	NPC602784
0.5156	Remote Similarity	NPC474484
0.5156	Remote Similarity	NPC474233
0.5156	Remote Similarity	NPC603388
0.5082	Remote Similarity	NPC245869
0.5082	Remote Similarity	NPC104387
0.5077	Remote Similarity	NPC175410

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC5767 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	6792
0.1-0.2	2289
0.2-0.3	63
0.3-0.4	5
0.4-0.5	1
0.5-0.6	0
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
		NPD

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