NPASS Compound

Natural Product: NPC21638

Natural Product ID	NPC21638
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	KXEMQEGRZWUKJS-RURTYGRKSA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL1329821
PubChem CID	72313
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000279] Alkaloids and derivatives [CHEMONTID:0001786] Yohimbine alkaloids

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 54 58 0 0 0 0 0 0 0 0999 V2000 7.2471 0.6213 -1.8216 C 0 0 0 0 0 0 0 0 0 0 0 0 5.9393 0.5693 -2.3470 O 0 0 0 0 0 0 0 0 0 0 0 0 4.9299 0.0651 -1.5402 C 0 0 0 0 0 0 0 0 0 0 0 0 5.1815 -0.3843 -0.2391 C 0 0 0 0 0 0 0 0 0 0 0 0 4.2027 -0.8802 0.5614 C 0 0 0 0 0 0 0 0 0 0 0 0 2.9026 -0.9600 0.1127 C 0 0 0 0 0 0 0 0 0 0 0 0 2.5935 -0.5252 -1.1794 C 0 0 0 0 0 0 0 0 0 0 0 0 3.6196 -0.0275 -1.9606 C 0 0 0 0 0 0 0 0 0 0 0 0 1.2738 -0.7174 -1.3445 N 0 0 0 0 0 0 0 0 0 0 0 0 0.7231 -1.2423 -0.2519 C 0 0 0 0 0 0 0 0 0 0 0 0 1.7245 -1.4035 0.6756 C 0 0 0 0 0 0 0 0 0 0 0 0 1.5087 -1.9650 2.0331 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0659 -2.1752 2.3503 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.7940 -1.3657 1.5489 N 0 0 0 0 0 0 0 0 0 0 0 0 -0.6620 -1.6579 0.1338 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.7157 -0.9677 -0.6724 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.6096 -0.1874 0.2644 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.7154 0.7925 1.0127 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.6744 0.0410 1.8003 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.1348 1.8447 0.1276 C 0 0 2 0 0 0 0 0 0 0 0 0 -1.0167 3.1683 0.8947 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.9028 2.1218 -1.0217 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.2301 1.7152 -1.0534 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.6199 0.6105 -0.4492 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.9997 0.1603 -0.4650 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.3359 -0.8992 0.1226 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.0166 0.8505 -1.1130 O 0 0 0 0 0 0 0 0 0 0 0 0 -7.3702 0.3845 -1.1133 C 0 0 0 0 0 0 0 0 0 0 0 0 7.9971 0.9288 -2.5641 H 0 0 0 0 0 0 0 0 0 0 0 0 7.5575 -0.4088 -1.4881 H 0 0 0 0 0 0 0 0 0 0 0 0 7.2852 1.2486 -0.9071 H 0 0 0 0 0 0 0 0 0 0 0 0 6.1867 -0.3223 0.1070 H 0 0 0 0 0 0 0 0 0 0 0 0 4.4475 -1.2132 1.5550 H 0 0 0 0 0 0 0 0 0 0 0 0 3.3912 0.3068 -2.9493 H 0 0 0 0 0 0 0 0 0 0 0 0 0.7813 -0.4701 -2.2394 H 0 0 0 0 0 0 0 0 0 0 0 0 2.0939 -2.9209 2.1534 H 0 0 0 0 0 0 0 0 0 0 0 0 1.9241 -1.2427 2.7788 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.1172 -1.9642 3.4128 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.1860 -3.2433 2.1411 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.7683 -2.7531 0.0041 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.2036 -0.3099 -1.4035 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.3177 -1.6856 -1.2793 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.0259 -0.8903 1.0013 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.4060 1.3196 1.7344 H 0 0 0 0 0 0 0 0 0 0 0 0 0.3463 0.4366 1.6012 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.8391 0.1908 2.8980 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.1018 1.6092 -0.2107 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.5344 3.9007 0.2174 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.0233 3.5657 1.1290 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.3760 3.0672 1.7836 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.0018 2.2805 -1.5710 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.9357 1.0929 -1.7726 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.4629 -0.6492 -1.4436 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.8256 0.5396 -0.0916 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 2 0 6 7 1 0 7 8 2 0 7 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 1 0 15 16 1 0 16 17 1 0 17 18 1 0 18 19 1 0 18 20 1 0 20 21 1 0 20 22 1 0 22 23 1 0 23 24 2 0 24 25 1 0 25 26 2 0 25 27 1 0 27 28 1 0 8 3 1 0 15 10 1 0 24 17 1 0 11 6 1 0 19 14 1 0 1 29 1 0 1 30 1 0 1 31 1 0 4 32 1 0 5 33 1 0 8 34 1 0 9 35 1 0 12 36 1 0 12 37 1 0 13 38 1 0 13 39 1 0 15 40 1 1 16 41 1 0 16 42 1 0 17 43 1 1 18 44 1 1 19 45 1 0 19 46 1 0 20 47 1 6 21 48 1 0 21 49 1 0 21 50 1 0 23 51 1 0 28 52 1 0 28 53 1 0 28 54 1 0 M END

Standard InCHIKey	KXEMQEGRZWUKJS-RURTYGRKSA-N
Standard InCHI	InChI=1S/C22H26N2O4/c1-12-17-10-24-7-6-15-14-5-4-13(26-2)8-19(14)23-21(15)20(24)9-16(17)18(11-28-12)22(25)27-3/h4-5,8,11-12,16-17,20,23H,6-7,9-10H2,1-3H3/t12-,16-,17-,20-/m0/s1
SMILES	COc1ccc2c(c1)[nH]c1c2CCN2[C@H]1C[C@H]1[C@@H](C2)[C@H](C)OC=C1C(=O)OC

Calculated Properties

Physi-Chem Properties

Molecular Weight:	382.19	Volume:	387.622 ? Van der Waals volume.
Dense:	0.986	LogP:	2.487 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.487 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.374 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	3.0	Rigid Bonds:	26.0
TPSA:	63.79 ? Topological Polar Surface Area.	H-Bond Acceptor:	6.0
H-Bond Donor:	1.0	Rings:	5.0
Heavy Atoms:	6.0

MedChem Properties

QED Drug-Likeness Score:	0.809	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	3.992	Fsp³:	0.5
MCE-18:	94.091 ? 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:	0	PAINS Alert:	0
Colloidal aggregators:	0.201	Fluc inhibitor:	0.5 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.76 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.247 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.002	Promiscuous compounds:	0.557

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.749	MDCK Permeability:	-4.727
Pgp-inhibitor:	0.038	Pgp-substrate:	0.733
PAMPA:	0.007 ? 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%):	0.412	30% Bioavailability (F30%):	0.368
50% Bioavailability (F50%):	0.962

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.498	MRP1:	1.0
Plasma Protein Binding (PPB):	89.489%	Volume Distribution (VD):	0.431
Fu:	10.269% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.632
OATP1B3 inhibitor:	0.842	BCRP inhibitor:	0.89
BSEP inhibitor:	0.997

ADMET: Metabolism

CYP1A2-inhibitor:	1.0	CYP1A2-substrate:	0.015
CYP2C19-inhibitor:	0.992	CYP2C19-substrate:	0.001
CYP2C9-inhibitor:	0.001	CYP2C9-substrate:	0.998
CYP2D6-inhibitor:	0.736	CYP2D6-substrate:	0.622
CYP3A4-inhibitor:	1.0	CYP3A4-substrate:	1.0
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.465
HLM stability:	0.059 ? 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):

10.756

Half-life (T1/2):

1.346

ADMET: Toxicity

hERG Blockers:	0.69	hERG Blockers (10um):	0.608
Human Hepatotoxicity (H-HT):	0.445	Drug-induced Liver Injury (DILI):	0.745
AMES Toxicity:	0.788	Rat Oral Acute Toxicity:	0.87
Maximum Recommended Daily Dose:	0.98	Skin Sensitization:	0.408
Carcinogencity:	0.822	Eye Corrosion:	0.0
Eye Irritation:	0.075	Respiratory Toxicity:	0.981
Drug-induced Neurotoxicity:	0.878	Ototoxicity:	0.519
Hematotoxicity:	0.363	Drug-induced Nephrotoxicity:	0.922
Genotoxicity:	0.983	RPMI-8226 Immunitoxicity:	0.109
A549 Cytotoxicity:	0.701	Hek293 Cytotoxicity:	0.703
BCF:	0.889 ? 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:	3.648 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.125 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.493 ? 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
NPO19809	Streptomyces roseoviolaceus	Species	Streptomycetaceae	Bacteria	n.a.	n.a.	n.a.	Database[COCONUT]
NPO2065	Eriostemon deserti	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO14210	Brugmansia arborea	Species	Solanaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO6602	Vinca major	Species	Apocynaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO3078	Gentiana pyrenaica	Species	Gentianaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO13490	Diospyros tricolor	Species	Ebenaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO12216	Gynura elliptica	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO13601	Relicina connivens	Species	Parmeliaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO25628.1	Abrus pulchellus subsp. cantoniensis	Subspecies	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO21627	Bambusa chungii	Species	Poaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO1409	Drymonia macrophylla	Species	Gesneriaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO25599	Gloxinia erinoides	Species	Gesneriaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO11862	Ostrinia nubilalis	Species	Crambidae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO14590	Ruta oreojasme	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO12216	Gynura elliptica	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO14590	Ruta oreojasme	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO14590	Ruta oreojasme	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO25628.1	Abrus pulchellus subsp. cantoniensis	Subspecies	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO14210	Brugmansia arborea	Species	Solanaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO14590	Ruta oreojasme	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO13490	Diospyros tricolor	Species	Ebenaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO21627	Bambusa chungii	Species	Poaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO2065	Eriostemon deserti	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO1409	Drymonia macrophylla	Species	Gesneriaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO25599	Gloxinia erinoides	Species	Gesneriaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO6602	Vinca major	Species	Apocynaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO12216	Gynura elliptica	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO11862	Ostrinia nubilalis	Species	Crambidae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO3078	Gentiana pyrenaica	Species	Gentianaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO19809	Streptomyces roseoviolaceus	Species	Streptomycetaceae	Bacteria	n.a.	n.a.	n.a.	Database[UNPD]
NPO25628.1	Abrus pulchellus subsp. cantoniensis	Subspecies	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO13601	Relicina connivens	Species	Parmeliaceae	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
Potency	9

Activity Type	# Activity
Individual protein	7
Protein-protein interaction	2

Molecular-level activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT282	Individual protein	MAP kinase ERK2	Homo sapiens	Potency	=	22387.2	nM	PubChem BioAssay data set
NPT198	Individual protein	Vitamin D receptor	Homo sapiens	Potency	n.a.	79432.8	nM	PubChem BioAssay data set
NPT55	Individual protein	Putative fructose-1,6-bisphosphate aldolase	Giardia intestinalis	Potency	=	14091.9	nM	PubChem BioAssay data set
NPT533	Protein-protein interaction	Runt-related transcription factor 1/Core-binding factor subunit beta	Homo sapiens	Potency	n.a.	39810.7	nM	PubChem BioAssay data set
NPT48	Individual protein	Lysine-specific demethylase 4D-like	Homo sapiens	Potency	=	25118.9	nM	PubChem BioAssay data set
NPT94	Individual protein	Aldehyde dehydrogenase 1A1	Homo sapiens	Potency	=	31622.8	nM	PubChem BioAssay data set
NPT51	Individual protein	Microtubule-associated protein tau	Homo sapiens	Potency	=	15848.9	nM	PubChem BioAssay data set
NPT51	Individual protein	Microtubule-associated protein tau	Homo sapiens	Potency	=	22387.2	nM	PubChem BioAssay data set
NPT197	Protein-protein interaction	Menin/Histone-lysine N-methyltransferase MLL	Homo sapiens	Potency	=	25118.9	nM	PubChem BioAssay data set

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

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 NPC21638 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	18706
0.1-0.2	30419
0.2-0.3	600
0.3-0.4	79
0.4-0.5	28
0.5-0.6	14
0.6-0.7	5
0.7-0.8	2
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
0.8101	Intermediate Similarity	NPC603895
0.7848	Intermediate Similarity	NPC312870
0.7848	Intermediate Similarity	NPC199851
0.7848	Intermediate Similarity	NPC294909
0.7848	Intermediate Similarity	NPC254240
0.7848	Intermediate Similarity	NPC128265
0.7848	Intermediate Similarity	NPC604675
0.6047	Remote Similarity	NPC486449
0.6047	Remote Similarity	NPC63199
0.6047	Remote Similarity	NPC111602
0.6047	Remote Similarity	NPC102338
0.6047	Remote Similarity	NPC196251
0.5862	Remote Similarity	NPC273374
0.573	Remote Similarity	NPC100898
0.573	Remote Similarity	NPC148183
0.573	Remote Similarity	NPC21084
0.573	Remote Similarity	NPC152768
0.573	Remote Similarity	NPC605270
0.5556	Remote Similarity	NPC131260
0.55	Remote Similarity	NPC100734
0.55	Remote Similarity	NPC88923
0.55	Remote Similarity	NPC315634
0.5288	Remote Similarity	NPC284685
0.5109	Remote Similarity	NPC107782
0.5109	Remote Similarity	NPC486454
0.5106	Remote Similarity	NPC293861

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC21638 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	3663
0.1-0.2	5375
0.2-0.3	101
0.3-0.4	3
0.4-0.5	3
0.5-0.6	3
0.6-0.7	0
0.7-0.8	2
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
0.7848	Intermediate Similarity	NPD4500	Approved
0.7848	Intermediate Similarity	NPD4501	Approved
0.55	Remote Similarity	NPD7803	Phase 4
0.5288	Remote Similarity	NPD7955	Phase 4
0.5288	Remote Similarity	NPD7956	Approved

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