NPASS Compound

Natural Product: NPC472401

Natural Product ID	NPC472401
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	DEJYWSYLQZVYOP-IKUTXWSVSA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL3400662
PubChem CID	n.a.
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 [CHEMONTID:0002906] Phorbol esters

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 72 75 0 0 0 0 0 0 0 0999 V2000 2.0200 -1.0481 -3.8905 C 0 0 0 0 0 0 0 0 0 0 0 0 1.5541 -0.9043 -2.4623 C 0 0 0 0 0 0 0 0 0 0 0 0 2.7400 -0.5702 -1.5930 C 0 0 0 0 0 0 0 0 0 0 0 0 3.3395 0.7305 -2.0842 C 0 0 0 0 0 0 0 0 0 0 0 0 2.3665 -0.5090 -0.1508 C 0 0 0 0 0 0 0 0 0 0 0 0 2.9513 -1.3058 0.6281 O 0 0 0 0 0 0 0 0 0 0 0 0 1.4441 0.3470 0.3581 O 0 0 0 0 0 0 0 0 0 0 0 0 1.0542 0.4448 1.6902 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0129 1.5294 2.0423 C 0 0 0 0 0 0 0 0 0 0 0 0 1.3631 1.6634 2.3676 C 0 0 0 0 0 0 0 0 0 0 0 0 1.7885 1.3876 3.8337 C 0 0 0 0 0 0 0 0 0 0 0 0 2.3461 2.6224 1.7217 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.9170 1.4107 0.9048 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.5723 1.9634 -0.3865 C 0 0 0 0 0 0 0 0 0 0 0 0 0.5262 2.5219 -0.5366 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.3961 1.9450 -1.5817 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.5958 1.4199 -1.8189 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.3694 0.6800 -0.7656 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.5293 -0.3344 -0.0638 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.5690 0.0626 0.9286 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.6089 -1.1171 1.1293 C 0 0 0 0 0 0 0 0 0 0 0 0 0.3995 -0.8007 2.2067 C 0 0 0 0 0 0 0 0 0 0 0 0 1.2888 -1.7670 2.5388 O 0 0 0 0 0 0 0 0 0 0 0 0 1.4576 -2.3547 3.7826 C 0 0 0 0 0 0 0 0 0 0 0 0 0.6898 -1.9189 4.6590 O 0 0 0 0 0 0 0 0 0 0 0 0 2.4287 -3.4004 4.1188 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.4632 -2.2846 1.5602 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.2490 0.0706 2.2008 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.1082 -1.2074 -1.1841 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.0946 -1.1862 -2.0670 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.1695 -0.3189 -1.5788 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.3666 -0.4347 -1.8093 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.0743 -1.9628 -3.3567 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.1476 1.4750 0.0183 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.7616 2.6554 -2.7537 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.5412 3.9841 -2.4006 O 0 0 0 0 0 0 0 0 0 0 0 0 1.8085 -0.1419 -4.4914 H 0 0 0 0 0 0 0 0 0 0 0 0 1.6106 -1.9624 -4.3679 H 0 0 0 0 0 0 0 0 0 0 0 0 3.1346 -1.1812 -3.9060 H 0 0 0 0 0 0 0 0 0 0 0 0 0.8030 -0.0929 -2.4190 H 0 0 0 0 0 0 0 0 0 0 0 0 1.0516 -1.8391 -2.1555 H 0 0 0 0 0 0 0 0 0 0 0 0 3.5014 -1.3532 -1.7678 H 0 0 0 0 0 0 0 0 0 0 0 0 4.4411 0.7175 -1.9531 H 0 0 0 0 0 0 0 0 0 0 0 0 3.1837 0.7315 -3.2002 H 0 0 0 0 0 0 0 0 0 0 0 0 2.8520 1.6213 -1.6907 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.6450 1.3212 2.9812 H 0 0 0 0 0 0 0 0 0 0 0 0 2.2205 2.2896 4.2887 H 0 0 0 0 0 0 0 0 0 0 0 0 2.5836 0.6088 3.8240 H 0 0 0 0 0 0 0 0 0 0 0 0 0.9323 0.9950 4.4121 H 0 0 0 0 0 0 0 0 0 0 0 0 2.8560 2.1889 0.8385 H 0 0 0 0 0 0 0 0 0 0 0 0 3.2197 2.8734 2.3988 H 0 0 0 0 0 0 0 0 0 0 0 0 1.9025 3.6308 1.5393 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.8177 2.0991 1.2114 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.0280 1.5293 -2.8021 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.3101 -0.9904 0.4708 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.0883 -1.2270 0.1907 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.1856 -0.5559 3.1293 H 0 0 0 0 0 0 0 0 0 0 0 0 2.9664 -3.6793 3.1872 H 0 0 0 0 0 0 0 0 0 0 0 0 3.1425 -3.0084 4.8520 H 0 0 0 0 0 0 0 0 0 0 0 0 1.9031 -4.3225 4.4757 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.1463 -1.9911 2.4049 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.8325 -3.1601 1.8525 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.1419 -2.6645 0.7729 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.9219 0.7956 2.1930 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.2102 -1.7881 -1.3512 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.1508 -3.0468 -3.1745 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.0545 -1.7823 -3.7958 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.8811 -1.6768 -4.0273 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.3163 2.3618 -0.3738 H 0 0 0 0 0 0 0 0 0 0 0 0 0.2431 2.1935 -2.8755 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.4042 2.5298 -3.6276 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.4335 4.4885 -3.2493 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 3 5 1 0 5 6 2 0 5 7 1 0 7 8 1 0 8 9 1 0 9 10 1 0 10 11 1 0 10 12 1 0 9 13 1 0 13 14 1 0 14 15 2 0 14 16 1 0 16 17 2 0 17 18 1 0 18 19 1 0 19 20 1 0 20 21 1 0 21 22 1 0 22 23 1 0 23 24 1 0 24 25 2 0 24 26 1 0 21 27 1 0 20 28 1 0 19 29 1 0 29 30 2 0 30 31 1 0 31 32 2 0 30 33 1 0 18 34 1 0 16 35 1 0 35 36 1 0 10 8 1 0 22 8 1 0 20 13 1 0 31 18 1 0 1 37 1 0 1 38 1 0 1 39 1 0 2 40 1 0 2 41 1 0 3 42 1 0 4 43 1 0 4 44 1 0 4 45 1 0 9 46 1 0 11 47 1 0 11 48 1 0 11 49 1 0 12 50 1 0 12 51 1 0 12 52 1 0 13 53 1 0 17 54 1 0 19 55 1 0 21 56 1 0 22 57 1 0 26 58 1 0 26 59 1 0 26 60 1 0 27 61 1 0 27 62 1 0 27 63 1 0 28 64 1 0 29 65 1 0 33 66 1 0 33 67 1 0 33 68 1 0 34 69 1 0 35 70 1 0 35 71 1 0 36 72 1 0 M END

Standard InCHIKey	DEJYWSYLQZVYOP-IKUTXWSVSA-N
Standard InCHI	InChI=1S/C27H36O9/c1-8-12(2)23(32)36-27-20(24(27,6)7)18-19(30)16(11-28)10-25(33)17(9-13(3)21(25)31)26(18,34)14(4)22(27)35-15(5)29/h9-10,12,14,17-18,20,22,28,33-34H,8,11H2,1-7H3/t12?,14-,17-,18+,20-,22-,25-,26+,27-/m1/s1
SMILES	CCC(C)C(=O)OC12C(C1(C)C)C3C(=O)C(=CC4(C(C3(C(C2OC(=O)C)C)O)C=C(C4=O)C)O)CO

Calculated Properties

Physi-Chem Properties

Molecular Weight:	504.24	Volume:	504.616 ? Van der Waals volume.
Dense:	0.999	LogP:	2.177 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.489 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.86 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	7.0	Rigid Bonds:	22.0
TPSA:	147.43 ? Topological Polar Surface Area.	H-Bond Acceptor:	9.0
H-Bond Donor:	3.0	Rings:	4.0
Heavy Atoms:	9.0

MedChem Properties

QED Drug-Likeness Score:	0.471	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	5.443	Fsp³:	0.704
MCE-18:	86.087 ? 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:	0.014	Fluc inhibitor:	0.0 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.01 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.093 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.305	Promiscuous compounds:	0.105

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.999	MDCK Permeability:	-4.783
Pgp-inhibitor:	0.032	Pgp-substrate:	0.461
PAMPA:	0.998 ? 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):	0.982
20% Bioavailability (F20%):	0.93	30% Bioavailability (F30%):	0.999
50% Bioavailability (F50%):	0.999

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.002	MRP1:	0.978
Plasma Protein Binding (PPB):	37.04%	Volume Distribution (VD):	-0.247
Fu:	65.289% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.273
OATP1B3 inhibitor:	0.978	BCRP inhibitor:	0.0
BSEP inhibitor:	0.936

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.016	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.007	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.999
CYP3A4-inhibitor:	0.974	CYP3A4-substrate:	0.0
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.995
HLM stability:	0.995 ? 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):

3.736

Half-life (T1/2):

1.733

ADMET: Toxicity

hERG Blockers:	0.056	hERG Blockers (10um):	0.277
Human Hepatotoxicity (H-HT):	0.567	Drug-induced Liver Injury (DILI):	0.525
AMES Toxicity:	0.718	Rat Oral Acute Toxicity:	0.448
Maximum Recommended Daily Dose:	0.467	Skin Sensitization:	0.274
Carcinogencity:	0.476	Eye Corrosion:	0.0
Eye Irritation:	0.015	Respiratory Toxicity:	0.554
Drug-induced Neurotoxicity:	0.657	Ototoxicity:	0.878
Hematotoxicity:	0.453	Drug-induced Nephrotoxicity:	0.29
Genotoxicity:	0.927	RPMI-8226 Immunitoxicity:	0.185
A549 Cytotoxicity:	0.069	Hek293 Cytotoxicity:	0.344
BCF:	0.658 ? 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:	3.568 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.745 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.848 ? 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
NPO2978	Croton tiglium	Species	Euphorbiaceae	Eukaryota	n.a.	seed	n.a.	PMID[21049973]
NPO2978	Croton tiglium	Species	Euphorbiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[23701597]
NPO2978	Croton tiglium	Species	Euphorbiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[25819096]
NPO2978	Croton tiglium	Species	Euphorbiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO2978	Croton tiglium	Species	Euphorbiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO2978	Croton tiglium	Species	Euphorbiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO2978	Croton tiglium	Species	Euphorbiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO2978	Croton tiglium	Species	Euphorbiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO2978	Croton tiglium	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
IC50	13

Activity Type	# Activity
Individual protein	2
Cell line	8
Non-molecular	3

Molecular-level activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT324	Individual protein	Cyclooxygenase-1	Ovis aries	IC50	>	50000.0	nM	PMID[24963714]
NPT31	Individual protein	Cyclooxygenase-2	Homo sapiens	IC50	>	50000.0	nM	PMID[24963714]

In vitro activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT111	Cell line	K562	Homo sapiens	IC50	=	7200.0	nM	PMID[23869482]
NPT112	Cell line	MOLT-4	Homo sapiens	IC50	=	10000.0	nM	PMID[22880631]
NPT83	Cell line	MCF7	Homo sapiens	IC50	>	50000.0	nM	PMID[22880631]
NPT165	Cell line	HeLa	Homo sapiens	IC50	=	10000.0	nM	PMID[21334794]
NPT90	Cell line	DU-145	Homo sapiens	IC50	=	11000.0	nM	PMID[22880631]
NPT81	Cell line	A549	Homo sapiens	IC50	>	50000.0	nM	PMID[22880631]
NPT2341	Cell line	NCI-H1975	Homo sapiens	IC50	=	10000.0	nM	PMID[22880631]
NPT2615	Cell line	HEK-293T	Homo sapiens	IC50	=	146600.0	nM	PMID[19715320]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	IC50	=	14000.0	nM	PMID[25819096]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	IC50	>	50000.0	nM	PMID[25819096]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	IC50	=	9900.0	nM	PMID[25819096]

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 NPC472401 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	16501
0.1-0.2	31315
0.2-0.3	1892
0.3-0.4	70
0.4-0.5	52
0.5-0.6	16
0.6-0.7	4
0.7-0.8	0
0.8-0.85	0
0.85-0.9	1
0.9-0.95	1
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.9333	High Similarity	NPC605797
0.875	High Similarity	NPC472399
0.7826	Intermediate Similarity	NPC607335
0.7826	Intermediate Similarity	NPC610849
0.75	Intermediate Similarity	NPC19464
0.75	Intermediate Similarity	NPC600879
0.75	Intermediate Similarity	NPC609967
0.7246	Intermediate Similarity	NPC486561
0.6933	Remote Similarity	NPC482200
0.6579	Remote Similarity	NPC605007
0.6338	Remote Similarity	NPC472758
0.6125	Remote Similarity	NPC486562
0.5976	Remote Similarity	NPC609007
0.5753	Remote Similarity	NPC472757
0.5616	Remote Similarity	NPC472397
0.56	Remote Similarity	NPC471125
0.5584	Remote Similarity	NPC471126
0.5556	Remote Similarity	NPC484334
0.5467	Remote Similarity	NPC609113
0.5333	Remote Similarity	NPC481522
0.525	Remote Similarity	NPC611949
0.519	Remote Similarity	NPC471128
0.5116	Remote Similarity	NPC482198
0.5067	Remote Similarity	NPC482406
0.5065	Remote Similarity	NPC481520
0.5063	Remote Similarity	NPC471127
0.5063	Remote Similarity	NPC481531
0.5062	Remote Similarity	NPC22628

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC472401 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	6409
0.1-0.2	2726
0.2-0.3	15
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