NPASS Compound

Natural Product: NPC474872

Natural Product ID	NPC474872
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	ZDINMEUMDNDKPM-UUIPYTTISA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL485826
PubChem CID	20839690
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0000259] Prenol lipids [CHEMONTID:0001551] Diterpenoids [CHEMONTID:0002875] Tigliane and ingenane diterpenoids

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 77 80 0 0 0 0 0 0 0 0999 V2000 4.0605 3.9355 -0.1854 C 0 0 0 0 0 0 0 0 0 0 0 0 3.3475 5.1395 -0.6171 C 0 0 0 0 0 0 0 0 0 0 0 0 2.0399 5.1202 -0.7264 C 0 0 0 0 0 0 0 0 0 0 0 0 1.2161 3.9491 -0.4404 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0412 4.0136 -0.5690 O 0 0 0 0 0 0 0 0 0 0 0 0 1.6940 2.7269 -0.0260 O 0 0 0 0 0 0 0 0 0 0 0 0 0.9485 1.5762 0.2628 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.0468 1.7089 1.3542 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.2349 0.8296 1.3540 C 0 0 1 0 0 0 0 0 0 0 0 0 -2.3267 1.5553 2.1566 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.6644 0.4442 -0.0047 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.4988 -0.3038 -0.6232 C 0 0 2 0 0 0 0 0 0 0 0 0 0.7473 0.4845 -0.6965 C 0 0 2 0 0 0 0 0 0 0 0 0 1.8390 0.3068 0.2526 C 0 0 2 0 0 0 0 0 0 0 0 0 1.8122 -0.5481 1.4792 C 0 0 0 0 0 0 0 0 0 0 0 0 3.2514 0.4396 -0.3180 C 0 0 0 0 0 0 0 0 0 0 0 0 3.8260 -0.8503 -0.2112 O 0 0 0 0 0 0 0 0 0 0 0 0 3.3073 -1.9610 -0.8233 C 0 0 0 0 0 0 0 0 0 0 0 0 2.2668 -1.8476 -1.5204 O 0 0 0 0 0 0 0 0 0 0 0 0 3.9403 -3.3037 -0.6880 C 0 0 0 0 0 0 0 0 0 0 0 0 3.1958 -4.3584 -1.4464 C 0 0 0 0 0 0 0 0 0 0 0 0 3.9595 -3.6972 0.7740 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.9895 -0.8585 -1.9047 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.8212 -1.9152 -2.0008 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.1893 -2.3070 -3.3826 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7614 -3.6352 -3.5841 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.4209 -2.7469 -0.9218 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.7492 -1.8360 0.2409 C 0 0 1 0 0 0 0 0 0 0 0 0 -2.8704 -0.3993 -0.1525 C 0 0 1 0 0 0 0 0 0 0 0 0 -4.1081 0.1241 0.4399 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.8510 -0.8720 0.8828 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.1750 -2.1461 0.6252 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.6041 -3.3212 0.6834 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.1822 -0.8010 1.5528 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.0072 -2.0787 1.3725 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.8813 1.5785 -0.7802 O 0 0 0 0 0 0 0 0 0 0 0 0 1.2868 6.3543 -1.1711 C 0 0 0 0 0 0 0 0 0 0 0 0 5.1481 4.2178 -0.0677 H 0 0 0 0 0 0 0 0 0 0 0 0 4.0787 3.1368 -0.9824 H 0 0 0 0 0 0 0 0 0 0 0 0 3.7438 3.5492 0.7924 H 0 0 0 0 0 0 0 0 0 0 0 0 3.8418 6.0899 -0.8652 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.4053 2.7741 1.3532 H 0 0 0 0 0 0 0 0 0 0 0 0 0.4433 1.6254 2.3709 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.9940 -0.0631 2.0009 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.0825 0.8715 2.5463 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.6986 2.4422 1.6319 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.7931 1.9596 3.0689 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.3195 -1.1809 0.0564 H 0 0 0 0 0 0 0 0 0 0 0 0 1.0267 0.7482 -1.7616 H 0 0 0 0 0 0 0 0 0 0 0 0 1.0193 -1.2820 1.5556 H 0 0 0 0 0 0 0 0 0 0 0 0 1.7566 0.0787 2.4164 H 0 0 0 0 0 0 0 0 0 0 0 0 2.7720 -1.1251 1.6307 H 0 0 0 0 0 0 0 0 0 0 0 0 3.2618 0.7290 -1.3782 H 0 0 0 0 0 0 0 0 0 0 0 0 3.8539 1.1183 0.3103 H 0 0 0 0 0 0 0 0 0 0 0 0 4.9853 -3.2915 -1.0877 H 0 0 0 0 0 0 0 0 0 0 0 0 3.0405 -4.0466 -2.5038 H 0 0 0 0 0 0 0 0 0 0 0 0 3.8543 -5.2566 -1.4975 H 0 0 0 0 0 0 0 0 0 0 0 0 2.2622 -4.6697 -0.9551 H 0 0 0 0 0 0 0 0 0 0 0 0 4.3675 -2.9038 1.4066 H 0 0 0 0 0 0 0 0 0 0 0 0 4.6586 -4.5793 0.8703 H 0 0 0 0 0 0 0 0 0 0 0 0 2.9750 -4.0821 1.1071 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.6983 -0.4337 -2.8440 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.7071 -1.6998 -4.1489 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.3010 -2.3402 -3.4800 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.3459 -4.2703 -3.0615 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.3160 -3.2553 -1.3297 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.6971 -3.5050 -0.5621 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.0793 -0.4243 -1.2692 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.3753 1.1570 0.5054 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.1862 -1.5541 2.3831 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.0008 -1.0944 0.8657 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.3822 0.2222 1.9425 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.5179 -1.9351 2.1972 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.8510 1.7690 -0.8740 H 0 0 0 0 0 0 0 0 0 0 0 0 1.9890 7.1203 -1.5650 H 0 0 0 0 0 0 0 0 0 0 0 0 0.8778 6.7812 -0.2117 H 0 0 0 0 0 0 0 0 0 0 0 0 0.4794 6.1029 -1.8697 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 2 0 4 6 1 0 7 6 1 6 7 8 1 0 8 9 1 0 9 10 1 0 9 11 1 0 11 12 1 0 12 13 1 0 13 14 1 0 14 15 1 1 14 16 1 0 16 17 1 0 17 18 1 0 18 19 2 0 18 20 1 0 20 21 1 0 20 22 1 0 12 23 1 0 23 24 2 0 24 25 1 0 25 26 1 0 24 27 1 0 27 28 1 0 28 29 1 0 29 30 1 0 30 31 2 0 31 32 1 0 32 33 2 0 31 34 1 0 28 35 1 1 11 36 1 6 3 37 1 0 13 7 1 0 32 28 1 0 14 7 1 0 29 11 1 0 1 38 1 0 1 39 1 0 1 40 1 0 2 41 1 0 8 42 1 0 8 43 1 0 9 44 1 1 10 45 1 0 10 46 1 0 10 47 1 0 12 48 1 1 13 49 1 6 15 50 1 0 15 51 1 0 15 52 1 0 16 53 1 0 16 54 1 0 20 55 1 0 21 56 1 0 21 57 1 0 21 58 1 0 22 59 1 0 22 60 1 0 22 61 1 0 23 62 1 0 25 63 1 0 25 64 1 0 26 65 1 0 27 66 1 0 27 67 1 0 29 68 1 6 30 69 1 0 34 70 1 0 34 71 1 0 34 72 1 0 35 73 1 0 36 74 1 0 37 75 1 0 37 76 1 0 37 77 1 0 M END

Standard InCHIKey	ZDINMEUMDNDKPM-UUIPYTTISA-N
Standard InCHI	InChI=1S/C29H40O8/c1-8-16(4)25(33)37-28-11-18(6)29(35)20(22(28)26(28,7)14-36-24(32)15(2)3)10-19(13-30)12-27(34)21(29)9-17(5)23(27)31/h8-10,15,18,20-22,30,34-35H,11-14H2,1-7H3/b16-8-/t18-,20+,21-,22-,26-,27-,28+,29-/m1/s1
SMILES	C/C=C(C(=O)O[C@@]12C[C@@H](C)[C@]3([C@H]([C@@H]1[C@@]2(C)COC(=O)C(C)C)C=C(CO)C[C@]1([C@H]3C=C(C1=O)C)O)O)/C

Calculated Properties

Physi-Chem Properties

Molecular Weight:	516.27	Volume:	530.417 ? Van der Waals volume.
Dense:	0.973	LogP:	1.855 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.04 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.49 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	8.0	Rigid Bonds:	22.0
TPSA:	130.36 ? Topological Polar Surface Area.	H-Bond Acceptor:	8.0
H-Bond Donor:	3.0	Rings:	4.0
Heavy Atoms:	8.0

MedChem Properties

QED Drug-Likeness Score:	0.279	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	5.375	Fsp³:	0.69
MCE-18:	84.286 ? 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:	0
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.111	Fluc inhibitor:	0.002 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.006 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.001 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.243	Promiscuous compounds:	0.445

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.046	MDCK Permeability:	-4.737
Pgp-inhibitor:	0.018	Pgp-substrate:	0.834
PAMPA:	0.972 ? 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):	0.087
20% Bioavailability (F20%):	0.949	30% Bioavailability (F30%):	0.994
50% Bioavailability (F50%):	0.998

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.024	MRP1:	0.992
Plasma Protein Binding (PPB):	71.683%	Volume Distribution (VD):	0.062
Fu:	32.12% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.945
OATP1B3 inhibitor:	0.846	BCRP inhibitor:	0.036
BSEP inhibitor:	0.996

ADMET: Metabolism

CYP1A2-inhibitor:	0.227	CYP1A2-substrate:	0.001
CYP2C19-inhibitor:	0.003	CYP2C19-substrate:	0.009
CYP2C9-inhibitor:	0.001	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.482
CYP3A4-inhibitor:	0.996	CYP3A4-substrate:	0.952
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.995
HLM stability:	0.706 ? 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):

5.603

Half-life (T1/2):

0.919

ADMET: Toxicity

hERG Blockers:	0.069	hERG Blockers (10um):	0.262
Human Hepatotoxicity (H-HT):	0.653	Drug-induced Liver Injury (DILI):	0.37
AMES Toxicity:	0.416	Rat Oral Acute Toxicity:	0.335
Maximum Recommended Daily Dose:	0.414	Skin Sensitization:	0.93
Carcinogencity:	0.665	Eye Corrosion:	0.032
Eye Irritation:	0.332	Respiratory Toxicity:	0.587
Drug-induced Neurotoxicity:	0.297	Ototoxicity:	0.665
Hematotoxicity:	0.64	Drug-induced Nephrotoxicity:	0.673
Genotoxicity:	0.713	RPMI-8226 Immunitoxicity:	0.095
A549 Cytotoxicity:	0.1	Hek293 Cytotoxicity:	0.151
BCF:	0.525 ? 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:	3.409 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.333 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.548 ? 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
NPO19062	Euphorbia coerulescens	Species	Euphorbiaceae	Eukaryota	latices	South African	n.a.	PMID[3236005]
NPO25960	Euphorbia triangularis	Species	Euphorbiaceae	Eukaryota	latices	South African	n.a.	PMID[3236005]
NPO32447	euphorbia ledienii	Species	Euphorbiaceae	Eukaryota	latices	South African	n.a.	PMID[3236005]
NPO19062	Euphorbia coerulescens	Species	Euphorbiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO25960	Euphorbia triangularis	Species	Euphorbiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO32447	euphorbia ledienii	Species	Euphorbiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO19062	Euphorbia coerulescens	Species	Euphorbiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO25960	Euphorbia triangularis	Species	Euphorbiaceae	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
Activity	2

Activity Type	# Activity
Organism	2

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

In vivo activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT32	Organism	Mus musculus	Mus musculus	Activity	=	0.25	nmol	PubChem BioAssay data set
NPT32	Organism	Mus musculus	Mus musculus	Activity	=	4.0	/nmol	PMID[21684166]

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 NPC474872 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	18108
0.1-0.2	30121
0.2-0.3	1496
0.3-0.4	59
0.4-0.5	38
0.5-0.6	23
0.6-0.7	9
0.7-0.8	0
0.8-0.85	1
0.85-0.9	0
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.8088	Intermediate Similarity	NPC475391
0.7692	Intermediate Similarity	NPC71889
0.7361	Intermediate Similarity	NPC474937
0.6866	Remote Similarity	NPC158523
0.6567	Remote Similarity	NPC153036
0.6538	Remote Similarity	NPC153651
0.6429	Remote Similarity	NPC475937
0.6389	Remote Similarity	NPC474871
0.622	Remote Similarity	NPC180640
0.6184	Remote Similarity	NPC482317
0.6145	Remote Similarity	NPC185876
0.6145	Remote Similarity	NPC19336
0.5946	Remote Similarity	NPC485736
0.5946	Remote Similarity	NPC277477
0.5946	Remote Similarity	NPC479003
0.5946	Remote Similarity	NPC485735
0.5921	Remote Similarity	NPC145182
0.5789	Remote Similarity	NPC482454
0.5769	Remote Similarity	NPC471128
0.5676	Remote Similarity	NPC174471
0.5658	Remote Similarity	NPC157252
0.557	Remote Similarity	NPC485732
0.557	Remote Similarity	NPC471126
0.5479	Remote Similarity	NPC96739
0.5432	Remote Similarity	NPC151216
0.5432	Remote Similarity	NPC89227
0.5395	Remote Similarity	NPC472397
0.5375	Remote Similarity	NPC477091
0.5325	Remote Similarity	NPC260786
0.5244	Remote Similarity	NPC600005
0.5205	Remote Similarity	NPC91189
0.519	Remote Similarity	NPC471125
0.5176	Remote Similarity	NPC472760
0.5135	Remote Similarity	NPC156252
0.5063	Remote Similarity	NPC472758

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC474872 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	6627
0.1-0.2	2514
0.2-0.3	9
0.3-0.4	0
0.4-0.5	0
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