NPASS Compound

Natural Product: NPC295691

Natural Product ID	NPC295691
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	3,9,10-Trimethoxy-6,8,13,13A-Tetrahydro-5H-Isoquinolino[2,1-B]Isoquinolin-2-Ol
IUPAC Name	3,9,10-trimethoxy-6,8,13,13a-tetrahydro-5H-isoquinolino[2,1-b]isoquinolin-2-ol
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL3780481
PubChem CID	10220
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000279] Alkaloids and derivatives [CHEMONTID:0001909] Protoberberine alkaloids 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 48 51 0 0 0 0 0 0 0 0999 V2000 -6.9611 -0.8283 -0.3228 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.2213 -0.1672 0.6571 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.8548 0.0518 0.5780 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.1371 -0.3969 -0.5263 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.7751 -0.1908 -0.6282 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.1033 -0.7144 -1.8569 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.6070 -0.8229 -1.5359 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.1878 0.4471 -1.0383 N 0 0 0 0 0 0 0 0 0 0 0 0 -0.6180 0.7226 0.3166 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.0796 0.4659 0.3594 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.7962 0.9059 1.4466 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.1622 0.7067 1.5630 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.8605 1.1606 2.6701 O 0 0 0 0 0 0 0 0 0 0 0 0 0.1307 -0.0732 1.3467 C 0 0 0 0 0 0 0 0 0 0 0 0 1.5715 -0.1789 1.0013 C 0 0 0 0 0 0 0 0 0 0 0 0 2.0951 0.2076 -0.2169 C 0 0 0 0 0 0 0 0 0 0 0 0 1.1881 0.7612 -1.2523 C 0 0 0 0 0 0 0 0 0 0 0 0 3.4236 0.1059 -0.5241 C 0 0 0 0 0 0 0 0 0 0 0 0 3.8982 0.4967 -1.7328 O 0 0 0 0 0 0 0 0 0 0 0 0 4.3625 1.7895 -2.0579 C 0 0 0 0 0 0 0 0 0 0 0 0 4.2811 -0.4045 0.4215 C 0 0 0 0 0 0 0 0 0 0 0 0 3.8147 -0.8149 1.6766 C 0 0 0 0 0 0 0 0 0 0 0 0 2.4581 -0.6882 1.9317 C 0 0 0 0 0 0 0 0 0 0 0 0 5.6318 -0.5215 0.1440 O 0 0 0 0 0 0 0 0 0 0 0 0 6.5185 -1.0447 1.1099 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.0016 -0.9298 0.0380 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.8913 -0.3684 -1.3275 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.5491 -1.8607 -0.4139 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.7074 -0.9143 -1.2961 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.5187 -1.6631 -2.2013 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.2153 0.0848 -2.6281 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.0819 -1.0351 -2.4697 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.4669 -1.6504 -0.8103 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.3988 1.8043 0.5035 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.2834 1.4264 2.2433 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.6644 1.7789 2.5045 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.3310 -1.0606 1.5495 H 0 0 0 0 0 0 0 0 0 0 0 0 0.0822 0.4844 2.3249 H 0 0 0 0 0 0 0 0 0 0 0 0 1.2918 1.8794 -1.2017 H 0 0 0 0 0 0 0 0 0 0 0 0 1.4791 0.3635 -2.2479 H 0 0 0 0 0 0 0 0 0 0 0 0 4.1973 1.9287 -3.1469 H 0 0 0 0 0 0 0 0 0 0 0 0 3.7905 2.5886 -1.5456 H 0 0 0 0 0 0 0 0 0 0 0 0 5.4290 1.9482 -1.7656 H 0 0 0 0 0 0 0 0 0 0 0 0 4.4817 -1.2176 2.4268 H 0 0 0 0 0 0 0 0 0 0 0 0 2.1170 -1.0155 2.9195 H 0 0 0 0 0 0 0 0 0 0 0 0 7.5274 -1.1759 0.6800 H 0 0 0 0 0 0 0 0 0 0 0 0 6.1235 -2.0246 1.4723 H 0 0 0 0 0 0 0 0 0 0 0 0 6.5806 -0.3460 1.9571 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 1 0 3 4 2 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 11 12 2 0 12 13 1 0 9 14 1 0 14 15 1 0 15 16 2 0 16 17 1 0 16 18 1 0 18 19 1 0 19 20 1 0 18 21 2 0 21 22 1 0 22 23 2 0 21 24 1 0 24 25 1 0 12 3 1 0 23 15 1 0 10 5 2 0 17 8 1 0 1 26 1 0 1 27 1 0 1 28 1 0 4 29 1 0 6 30 1 0 6 31 1 0 7 32 1 0 7 33 1 0 9 34 1 0 11 35 1 0 13 36 1 0 14 37 1 0 14 38 1 0 17 39 1 0 17 40 1 0 20 41 1 0 20 42 1 0 20 43 1 0 22 44 1 0 23 45 1 0 25 46 1 0 25 47 1 0 25 48 1 0 M END

Standard InCHIKey	KDFKJOFJHSVROC-UHFFFAOYSA-N
Standard InCHI	InChI=1S/C20H23NO4/c1-23-18-5-4-12-8-16-14-10-17(22)19(24-2)9-13(14)6-7-21(16)11-15(12)20(18)25-3/h4-5,9-10,16,22H,6-8,11H2,1-3H3
SMILES	COc1cc2CCN3C(c2cc1O)Cc1c(C3)c(OC)c(cc1)OC

Calculated Properties

Physi-Chem Properties

Molecular Weight:	341.16	Volume:	350.589 ? Van der Waals volume.
Dense:	0.973	LogP:	1.519 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	1.841 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-2.133 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	3.0	Rigid Bonds:	21.0
TPSA:	51.16 ? Topological Polar Surface Area.	H-Bond Acceptor:	5.0
H-Bond Donor:	1.0	Rings:	4.0
Heavy Atoms:	5.0

MedChem Properties

QED Drug-Likeness Score:	0.93	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	2.93	Fsp³:	0.4
MCE-18:	73.857 ? 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:	Rejected
Golden Triangle Rule:	Rejected	BMS Rule:	0
Chelating Alert:	1	PAINS Alert:	0
Colloidal aggregators:	0.241	Fluc inhibitor:	0.06 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.359 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.441 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.001	Promiscuous compounds:	0.039

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.824	MDCK Permeability:	-4.72
Pgp-inhibitor:	0.055	Pgp-substrate:	0.123
PAMPA:	0.011 ? 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):	0.002
20% Bioavailability (F20%):	0.046	30% Bioavailability (F30%):	0.097
50% Bioavailability (F50%):	0.946

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.795	MRP1:	0.976
Plasma Protein Binding (PPB):	78.213%	Volume Distribution (VD):	-0.094
Fu:	19.873% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.956
OATP1B3 inhibitor:	0.997	BCRP inhibitor:	0.639
BSEP inhibitor:	0.906

ADMET: Metabolism

CYP1A2-inhibitor:	1.0	CYP1A2-substrate:	0.072
CYP2C19-inhibitor:	0.999	CYP2C19-substrate:	0.001
CYP2C9-inhibitor:	0.996	CYP2C9-substrate:	0.983
CYP2D6-inhibitor:	0.998	CYP2D6-substrate:	0.369
CYP3A4-inhibitor:	0.806	CYP3A4-substrate:	0.897
CYP2B6-substrate:	0.988	CYP2C8-inhibitor:	0.723
HLM stability:	0.62 ? 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):

5.529

Half-life (T1/2):

2.232

ADMET: Toxicity

hERG Blockers:	0.418	hERG Blockers (10um):	0.66
Human Hepatotoxicity (H-HT):	0.472	Drug-induced Liver Injury (DILI):	0.034
AMES Toxicity:	0.65	Rat Oral Acute Toxicity:	0.533
Maximum Recommended Daily Dose:	0.702	Skin Sensitization:	0.836
Carcinogencity:	0.824	Eye Corrosion:	0.002
Eye Irritation:	0.264	Respiratory Toxicity:	0.949
Drug-induced Neurotoxicity:	0.479	Ototoxicity:	0.641
Hematotoxicity:	0.164	Drug-induced Nephrotoxicity:	0.106
Genotoxicity:	0.234	RPMI-8226 Immunitoxicity:	0.06
A549 Cytotoxicity:	0.199	Hek293 Cytotoxicity:	0.505
BCF:	1.453 ? 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:	3.937 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.26 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.556 ? 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
NPO23628	Imperata cylindrica	Species	Poaceae	Eukaryota	n.a.	n.a.	n.a.	DOI[10.3390/plants9101397]
NPO23628	Imperata cylindrica	Species	Poaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[16499335]
NPO25345	Corydalis ternata	Species	Papaveraceae	Eukaryota	tubers	n.a.	n.a.	PMID[20594848]
NPO827	Corydalis yanhusuo	Species	Papaveraceae	Eukaryota	n.a.	n.a.	n.a.	PMID[22737858]
NPO827	Corydalis yanhusuo	Species	Papaveraceae	Eukaryota	n.a.	n.a.	n.a.	PMID[23194502]
NPO13962	Corydalis turtschaninovii	Species	Papaveraceae	Eukaryota	n.a.	rhizome	n.a.	PMID[25277281]
NPO13962	Corydalis turtschaninovii	Species	Papaveraceae	Eukaryota	n.a.	tuber	n.a.	PMID[25670016]
NPO827	Corydalis yanhusuo	Species	Papaveraceae	Eukaryota	n.a.	n.a.	n.a.	PMID[32058719]
NPO23628	Imperata cylindrica	Species	Poaceae	Eukaryota	n.a.	rhizome	n.a.	PMID[7714541]
NPO23628	Imperata cylindrica	Species	Poaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[7760071]
NPO23628	Imperata cylindrica	Species	Poaceae	Eukaryota	n.a.	rhizome	n.a.	PMID[7798964]
NPO23628	Imperata cylindrica	Species	Poaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[7964801]
NPO827	Corydalis yanhusuo	Species	Papaveraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO23628	Imperata cylindrica	Species	Poaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO2341	Fibraurea recisa	Species	Menispermaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO13962	Corydalis turtschaninovii	Species	Papaveraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO25345	Corydalis ternata	Species	Papaveraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO2341	Fibraurea recisa	Species	Menispermaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO23628	Imperata cylindrica	Species	Poaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO827	Corydalis yanhusuo	Species	Papaveraceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO2341	Fibraurea recisa	Species	Menispermaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO23628	Imperata cylindrica	Species	Poaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO827	Corydalis yanhusuo	Species	Papaveraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO827	Corydalis yanhusuo	Species	Papaveraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO31048	Papaver sommiferum	Species	Papaveraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO23628	Imperata cylindrica	Species	Poaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO23628	Imperata cylindrica	Species	Poaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO13962	Corydalis turtschaninovii	Species	Papaveraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO25345	Corydalis ternata	Species	Papaveraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO827	Corydalis yanhusuo	Species	Papaveraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO2341	Fibraurea recisa	Species	Menispermaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO25345	Corydalis ternata	Species	Papaveraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO827	Corydalis yanhusuo	Species	Papaveraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO13962	Corydalis turtschaninovii	Species	Papaveraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO23628	Imperata cylindrica	Species	Poaceae	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
Ki	5
Ratio Ki	4
IC50	1

Activity Type	# Activity
Individual protein	4
Cell line	1
Others	5

Molecular-level activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT296	Individual protein	Sigma opioid receptor	Homo sapiens	Ki	=	106.0	nM	PMID[27032890]
NPT244	Individual protein	Dopamine D3 receptor	Homo sapiens	Ki	=	37.0	nM	PMID[27032890]
NPT243	Individual protein	Dopamine D2 receptor	Homo sapiens	Ki	=	102.0	nM	PMID[27032890]
NPT242	Individual protein	Dopamine D1 receptor	Homo sapiens	Ki	=	15.0	nM	PMID[27032890]

In vitro activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT82	Cell line	MDA-MB-231	Homo sapiens	IC50	=	178000.0	nM	PMID[27032890]
NPT2	Others	Unspecified	n.a.	Ki	=	1.0	nM	PMID[27032890]
NPT2	Others	Unspecified	n.a.	Ratio Ki	=	6.8	n.a.	PMID[27032890]
NPT2	Others	Unspecified	n.a.	Ratio Ki	=	2.5	n.a.	PMID[27032890]
NPT2	Others	Unspecified	n.a.	Ratio Ki	=	2.8	n.a.	PMID[27032890]
NPT2	Others	Unspecified	n.a.	Ratio Ki	=	106.0	n.a.	PMID[27032890]

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 NPC295691 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	27457
0.1-0.2	19552
0.2-0.3	2521
0.3-0.4	250
0.4-0.5	33
0.5-0.6	18
0.6-0.7	9
0.7-0.8	1
0.8-0.85	1
0.85-0.9	2
0.9-0.95	0
0.95-1	2

Similarity Score	Similarity Level	Natural Product ID
1.0	High Similarity	NPC207757
1.0	High Similarity	NPC54379
0.8909	High Similarity	NPC204828
0.8909	High Similarity	NPC5238
0.8333	Intermediate Similarity	NPC232514
0.7586	Intermediate Similarity	NPC189266
0.7586	Intermediate Similarity	NPC2413
0.7586	Intermediate Similarity	NPC110416
0.75	Intermediate Similarity	NPC210437
0.75	Intermediate Similarity	NPC16107
0.75	Intermediate Similarity	NPC106295
0.7368	Intermediate Similarity	NPC51957
0.7213	Intermediate Similarity	NPC264850
0.7167	Intermediate Similarity	NPC249797
0.7167	Intermediate Similarity	NPC193949
0.7018	Intermediate Similarity	NPC88249
0.6885	Remote Similarity	NPC216459
0.6885	Remote Similarity	NPC41178
0.6885	Remote Similarity	NPC138487
0.6721	Remote Similarity	NPC172765
0.629	Remote Similarity	NPC39701
0.629	Remote Similarity	NPC184026
0.625	Remote Similarity	NPC326205
0.6167	Remote Similarity	NPC220858
0.6129	Remote Similarity	NPC151895
0.5938	Remote Similarity	NPC276588
0.5938	Remote Similarity	NPC127674
0.5938	Remote Similarity	NPC31311
0.5938	Remote Similarity	NPC278799
0.5938	Remote Similarity	NPC234392
0.5821	Remote Similarity	NPC606650
0.5758	Remote Similarity	NPC312025
0.5714	Remote Similarity	NPC147390
0.5714	Remote Similarity	NPC428
0.5507	Remote Similarity	NPC276944
0.5507	Remote Similarity	NPC238530
0.5385	Remote Similarity	NPC321505
0.5385	Remote Similarity	NPC179825
0.5303	Remote Similarity	NPC7467
0.5224	Remote Similarity	NPC469817
0.5135	Remote Similarity	NPC480592
0.5082	Remote Similarity	NPC34559
0.5082	Remote Similarity	NPC128019

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC295691 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	4019
0.1-0.2	4894
0.2-0.3	221
0.3-0.4	13
0.4-0.5	1
0.5-0.6	1
0.6-0.7	0
0.7-0.8	1
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
0.75	Intermediate Similarity	NPD4584	Phase 2
0.5072	Remote Similarity	NPD4010	Discontinued

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