NPASS Compound

Natural Product: NPC311166

Natural Product ID	NPC311166
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Caseargrewins H
IUPAC Name	[(1S,3R,5R,6aS,7R,8R,10aS)-1,3-diacetyloxy-7,8-dimethyl-7-[(2Z)-3-methylpenta-2,4-dienyl]-1,3,5,6,6a,8,9,10-octahydrobenzo[d][2]benzofuran-5-yl] hexanoate
Synonyms	caseargrewins H
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL231313
PubChem CID	16756887
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0000259] Prenol lipids [CHEMONTID:0001551] Diterpenoids [CHEMONTID:0001757] Colensane and clerodane 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 81 83 0 0 0 0 0 0 0 0999 V2000 8.4484 1.2902 0.3905 C 0 0 0 0 0 0 0 0 0 0 0 0 6.9402 1.3945 0.1461 C 0 0 0 0 0 0 0 0 0 0 0 0 6.6495 1.2499 -1.3259 C 0 0 0 0 0 0 0 0 0 0 0 0 5.1917 1.3664 -1.5988 C 0 0 0 0 0 0 0 0 0 0 0 0 4.4395 0.2855 -0.8656 C 0 0 0 0 0 0 0 0 0 0 0 0 2.9715 0.3778 -1.1468 C 0 0 0 0 0 0 0 0 0 0 0 0 2.5761 1.2811 -1.9053 O 0 0 0 0 0 0 0 0 0 0 0 0 2.1078 -0.5067 -0.5826 O 0 0 0 0 0 0 0 0 0 0 0 0 0.7212 -0.4365 -0.8356 C 0 0 1 0 0 0 0 0 0 0 0 0 0.3318 -1.7888 -1.3837 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8647 -2.2653 -1.1941 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.5412 -3.5180 -1.5832 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.6183 -4.5618 -1.8636 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.6032 -5.1707 -3.0901 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.4159 -4.7964 -3.9681 O 0 0 0 0 0 0 0 0 0 0 0 0 0.3656 -6.2579 -3.3668 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.2709 -3.8461 -0.4761 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.4839 -2.7464 0.3416 C 0 0 2 0 0 0 0 0 0 0 0 0 -1.9666 -1.5351 -0.4497 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.4769 -0.4423 0.4318 C 0 0 1 0 0 0 0 0 0 0 0 0 0.0314 -0.3759 0.5092 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.1609 0.8691 0.3173 C 0 0 2 0 0 0 0 0 0 0 0 0 -1.7786 1.7014 -0.8657 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.8603 1.7123 1.5437 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.5380 3.0260 1.4820 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.9543 4.2031 1.4947 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.5167 4.3328 1.5749 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0655 5.5224 1.5868 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.7718 5.4680 1.4258 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.6509 0.6070 0.2237 C 0 0 1 0 0 0 0 0 0 0 0 0 -4.0316 -0.1868 -0.9798 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.0260 -1.1746 -1.4348 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.2594 0.0579 1.4648 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.8538 -2.8820 1.5772 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.6110 -2.9561 2.7302 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.8743 -2.9075 2.7132 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.9914 -3.0987 4.0777 C 0 0 0 0 0 0 0 0 0 0 0 0 8.9124 0.7998 -0.4851 H 0 0 0 0 0 0 0 0 0 0 0 0 8.6422 0.7638 1.3407 H 0 0 0 0 0 0 0 0 0 0 0 0 8.8656 2.3173 0.4965 H 0 0 0 0 0 0 0 0 0 0 0 0 6.4858 0.5388 0.7139 H 0 0 0 0 0 0 0 0 0 0 0 0 6.5223 2.3429 0.4922 H 0 0 0 0 0 0 0 0 0 0 0 0 7.0321 0.2463 -1.6758 H 0 0 0 0 0 0 0 0 0 0 0 0 7.2390 2.0245 -1.8855 H 0 0 0 0 0 0 0 0 0 0 0 0 4.9751 1.3625 -2.6877 H 0 0 0 0 0 0 0 0 0 0 0 0 4.7928 2.3381 -1.1863 H 0 0 0 0 0 0 0 0 0 0 0 0 4.5710 0.4335 0.2304 H 0 0 0 0 0 0 0 0 0 0 0 0 4.8523 -0.6863 -1.1864 H 0 0 0 0 0 0 0 0 0 0 0 0 0.5280 0.3882 -1.5031 H 0 0 0 0 0 0 0 0 0 0 0 0 1.0679 -2.3377 -1.9312 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.1806 -3.3198 -2.4737 H 0 0 0 0 0 0 0 0 0 0 0 0 1.2963 -6.1758 -2.7918 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.1158 -7.2237 -3.1230 H 0 0 0 0 0 0 0 0 0 0 0 0 0.6409 -6.2354 -4.4470 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.5800 -2.6959 0.4982 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.7609 -0.7749 1.4903 H 0 0 0 0 0 0 0 0 0 0 0 0 0.3565 0.3879 1.1820 H 0 0 0 0 0 0 0 0 0 0 0 0 0.3378 -1.3541 1.0050 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.8118 2.2420 -0.6963 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.5276 2.5337 -1.0251 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.6985 1.1962 -1.8208 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.7841 1.8792 1.5626 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.1010 1.1643 2.4812 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.6432 3.0815 1.4200 H 0 0 0 0 0 0 0 0 0 0 0 0 0.1168 3.4825 1.6276 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.4954 6.4414 1.5379 H 0 0 0 0 0 0 0 0 0 0 0 0 1.1338 5.6029 1.6465 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.8373 5.2372 1.4723 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.4335 6.1923 2.1951 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.5221 5.9250 0.4461 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.1004 1.6390 0.0718 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.0130 -0.6703 -0.7793 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.2439 0.4939 -1.8587 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.5949 -2.1237 -1.6836 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.5936 -0.9204 -2.4511 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.9920 0.7796 1.9246 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.9063 -0.8328 1.2107 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.5674 -0.2236 2.2541 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.6395 -2.6322 4.8519 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.9601 -2.7257 4.1196 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.9853 -4.1940 4.3055 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 1 0 3 4 1 0 4 5 1 0 5 6 1 0 6 7 2 0 6 8 1 0 8 9 1 0 9 10 1 0 10 11 2 0 11 12 1 0 12 13 1 0 13 14 1 0 14 15 2 0 14 16 1 0 12 17 1 0 17 18 1 0 18 19 1 0 19 20 1 0 20 21 1 0 20 22 1 0 22 23 1 6 22 24 1 0 24 25 1 0 25 26 2 0 26 27 1 0 27 28 2 0 26 29 1 0 22 30 1 0 30 31 1 0 31 32 1 0 30 33 1 0 18 34 1 0 34 35 1 0 35 36 2 0 35 37 1 0 21 9 1 0 19 11 1 0 19 32 1 6 1 38 1 0 1 39 1 0 1 40 1 0 2 41 1 0 2 42 1 0 3 43 1 0 3 44 1 0 4 45 1 0 4 46 1 0 5 47 1 0 5 48 1 0 9 49 1 6 10 50 1 0 12 51 1 6 16 52 1 0 16 53 1 0 16 54 1 0 18 55 1 1 20 56 1 1 21 57 1 0 21 58 1 0 23 59 1 0 23 60 1 0 23 61 1 0 24 62 1 0 24 63 1 0 25 64 1 0 27 65 1 0 28 66 1 0 28 67 1 0 29 68 1 0 29 69 1 0 29 70 1 0 30 71 1 6 31 72 1 0 31 73 1 0 32 74 1 0 32 75 1 0 33 76 1 0 33 77 1 0 33 78 1 0 37 79 1 0 37 80 1 0 37 81 1 0 M END

Standard InCHIKey	BCVXZPHRQXQURQ-RYILYFAJSA-N
Standard InCHI	InChI=1S/C30H44O7/c1-8-10-11-12-26(33)36-23-17-24-27(34-21(5)31)37-28(35-22(6)32)30(24)16-14-20(4)29(7,25(30)18-23)15-13-19(3)9-2/h9,13,17,20,23,25,27-28H,2,8,10-12,14-16,18H2,1,3-7H3/b19-13-/t20-,23+,25+,27+,28-,29-,30-/m1/s1
SMILES	CCCCCC(=O)O[C@H]1C=C2[C@@H](OC(=O)C)O[C@H]([C@]32[C@@H](C1)[C@](C)(C/C=C(C=C)/C)[C@@H](CC3)C)OC(=O)C

Calculated Properties

Physi-Chem Properties

Molecular Weight:	516.31	Volume:	547.479 ? Van der Waals volume.
Dense:	0.943	LogP:	4.333 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.704 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.58 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	13.0	Rigid Bonds:	20.0
TPSA:	88.13 ? Topological Polar Surface Area.	H-Bond Acceptor:	7.0
H-Bond Donor:	0.0	Rings:	3.0
Heavy Atoms:	7.0

MedChem Properties

QED Drug-Likeness Score:	0.113	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	5.509	Fsp³:	0.7
MCE-18:	84.804 ? 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:	0.676	Fluc inhibitor:	0.002 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.005 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.003 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.474	Promiscuous compounds:	0.582

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.018	MDCK Permeability:	-4.795
Pgp-inhibitor:	0.985	Pgp-substrate:	0.924
PAMPA:	0.213 ? 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):	0.008
20% Bioavailability (F20%):	0.992	30% Bioavailability (F30%):	0.993
50% Bioavailability (F50%):	1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.019	MRP1:	0.996
Plasma Protein Binding (PPB):	96.603%	Volume Distribution (VD):	-0.212
Fu:	4.037% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.98
OATP1B3 inhibitor:	0.484	BCRP inhibitor:	0.576
BSEP inhibitor:	1.0

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.526
CYP2C19-inhibitor:	0.123	CYP2C19-substrate:	0.012
CYP2C9-inhibitor:	0.002	CYP2C9-substrate:	0.056
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.011
CYP3A4-inhibitor:	0.008	CYP3A4-substrate:	0.608
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.998
HLM stability:	0.988 ? 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):

7.183

Half-life (T1/2):

0.526

ADMET: Toxicity

hERG Blockers:	0.15	hERG Blockers (10um):	0.518
Human Hepatotoxicity (H-HT):	0.657	Drug-induced Liver Injury (DILI):	0.875
AMES Toxicity:	0.892	Rat Oral Acute Toxicity:	0.908
Maximum Recommended Daily Dose:	0.987	Skin Sensitization:	0.994
Carcinogencity:	0.516	Eye Corrosion:	0.004
Eye Irritation:	0.102	Respiratory Toxicity:	0.832
Drug-induced Neurotoxicity:	0.89	Ototoxicity:	0.4
Hematotoxicity:	0.474	Drug-induced Nephrotoxicity:	0.832
Genotoxicity:	0.734	RPMI-8226 Immunitoxicity:	0.201
A549 Cytotoxicity:	0.813	Hek293 Cytotoxicity:	0.393
BCF:	1.195 ? 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:	4.289 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	6.171 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	5.679 ? 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
NPO31460	Casearia grewiifolia	Species	Salicaceae	Eukaryota	n.a.	bark	n.a.	PMID[15730240]
NPO31460	Casearia grewiifolia	Species	Salicaceae	Eukaryota	bark	in the campus of Khon Kaen University, Khon Kaen, Thailand	2001-SEP	PMID[15730240]
NPO31460	Casearia grewiifolia	Species	Salicaceae	Eukaryota	Fruits	n.a.	n.a.	PMID[17567069]
NPO31460	Casearia grewiifolia	Species	Salicaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[26516994]
NPO31460	Casearia grewiifolia	Species	Salicaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]

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	3

Activity Type	# Activity
Cell line	2
Non-molecular	1

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
NPT91	Cell line	KB	Homo sapiens	IC50	=	0.88	ug.mL-1	PMID[8277309]
NPT639	Cell line	NCI-H187	Homo sapiens	IC50	=	0.54	ug.mL-1	PMID[12398531]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	IC50	=	0.21	ug.mL-1	PMID[17567069]

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 NPC311166 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	23334
0.1-0.2	23634
0.2-0.3	2736
0.3-0.4	49
0.4-0.5	66
0.5-0.6	25
0.6-0.7	8
0.7-0.8	0
0.8-0.85	0
0.85-0.9	0
0.9-0.95	1
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.9138	High Similarity	NPC88507
0.6714	Remote Similarity	NPC488964
0.6714	Remote Similarity	NPC184512
0.64	Remote Similarity	NPC208293
0.625	Remote Similarity	NPC252296
0.6212	Remote Similarity	NPC603601
0.6119	Remote Similarity	NPC98112
0.6056	Remote Similarity	NPC201880
0.6029	Remote Similarity	NPC606965
0.5946	Remote Similarity	NPC119550
0.5942	Remote Similarity	NPC600724
0.5857	Remote Similarity	NPC488235
0.5783	Remote Similarity	NPC100420
0.5753	Remote Similarity	NPC609715
0.5694	Remote Similarity	NPC473204
0.5634	Remote Similarity	NPC602188
0.5625	Remote Similarity	NPC172867
0.5616	Remote Similarity	NPC316974
0.5616	Remote Similarity	NPC134270
0.5616	Remote Similarity	NPC81567
0.5616	Remote Similarity	NPC488652
0.5405	Remote Similarity	NPC329623
0.5405	Remote Similarity	NPC609711
0.5333	Remote Similarity	NPC330003
0.5333	Remote Similarity	NPC470321
0.5333	Remote Similarity	NPC264867
0.5333	Remote Similarity	NPC473207
0.5205	Remote Similarity	NPC488659
0.5205	Remote Similarity	NPC604149
0.52	Remote Similarity	NPC311223
0.52	Remote Similarity	NPC488654
0.5181	Remote Similarity	NPC109376
0.5132	Remote Similarity	NPC217921
0.5132	Remote Similarity	NPC135015

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC311166 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	7422
0.1-0.2	1681
0.2-0.3	47
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