NPASS Compound

Natural Product: NPC558996

Natural Product ID	NPC558996
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	3-[(3~{S},5~{S},8~{R},9~{R},10~{R},13~{R},14~{S},17~{S})-3-[(2~{S},4~{R},5~{S},6~{R})-5-amino-4-methoxy-6-methyl-tetrahydropyran-2-yl]oxy-14-hydroxy-10,13-dimethyl-1,2,3,4,5,6,7,8,9,11,12,15,16,17-tetradecahydrocyclopenta[a]phenanthren-17-yl]-2~{H}-furan-5-one
IUPAC Name	3-[(3~{S},5~{S},8~{R},9~{R},10~{R},13~{R},14~{S},17~{S})-3-[(2~{S},4~{R},5~{S},6~{R})-5-amino-4-methoxy-6-methyl-tetrahydropyran-2-yl]oxy-14-hydroxy-10,13-dimethyl-1,2,3,4,5,6,7,8,9,11,12,15,16,17-tetradecahydrocyclopenta[a]phenanthren-17-yl]-2~{H}-furan-5-one
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	n.a.
Chemical Classification	CHEMONTID:0000000 [Organic compounds]

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 84 89 0 0 0 0 0 0 0 0999 V2000 7.8902 -2.3192 -0.8599 C 0 0 0 0 0 0 0 0 0 0 0 0 7.0517 -1.2449 -0.5907 O 0 0 0 0 0 0 0 0 0 0 0 0 6.8193 -1.1394 0.7551 C 0 0 2 0 0 0 0 0 0 0 0 0 5.3595 -1.3131 1.1128 C 0 0 0 0 0 0 0 0 0 0 0 0 4.6179 -0.0507 0.6766 C 0 0 1 0 0 0 0 0 0 0 0 0 3.2700 -0.1256 0.9575 O 0 0 0 0 0 0 0 0 0 0 0 0 2.4449 -0.0036 -0.1246 C 0 0 1 0 0 0 0 0 0 0 0 0 1.6857 -1.3132 -0.2929 C 0 0 0 0 0 0 0 0 0 0 0 0 0.3193 -1.1220 0.3232 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.5169 -0.2321 -0.6131 C 0 0 2 0 0 0 0 0 0 0 0 0 -0.8656 -1.1024 -1.7965 C 0 0 0 0 0 0 0 0 0 0 0 0 0.3289 0.9079 -1.0024 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.3608 2.2096 -1.2237 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7981 1.8971 -1.5956 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.4258 1.3823 -0.2851 C 0 0 2 0 0 0 0 0 0 0 0 0 -1.7593 0.1583 0.2015 C 0 0 1 0 0 0 0 0 0 0 0 0 -2.5641 -1.0656 0.3916 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.0043 -0.9801 -0.0190 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.6302 0.3462 0.3376 C 0 0 2 0 0 0 0 0 0 0 0 0 -4.5425 0.6596 1.8000 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.0142 0.4391 -0.2266 C 0 0 2 0 0 0 0 0 0 0 0 0 -6.9081 -0.6352 0.1938 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.5056 -1.5418 -0.5583 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.3130 -2.4314 0.2626 C 0 0 0 0 0 0 0 0 0 0 0 0 -9.0054 -3.4009 -0.1641 O 0 0 0 0 0 0 0 0 0 0 0 0 -8.1734 -2.0107 1.5823 O 0 0 0 0 0 0 0 0 0 0 0 0 -7.3192 -0.9083 1.5927 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.7696 0.4827 -1.7063 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.3456 1.0274 -1.8850 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.8858 1.3595 -0.5041 C 0 0 2 0 0 0 0 0 0 0 0 0 -4.4813 2.6064 -0.1899 O 0 0 0 0 0 0 0 0 0 0 0 0 1.4861 1.1599 -0.0307 C 0 0 0 0 0 0 0 0 0 0 0 0 5.1201 1.0634 1.3564 O 0 0 0 0 0 0 0 0 0 0 0 0 6.4195 1.3289 1.0015 C 0 0 2 0 0 0 0 0 0 0 0 0 6.5733 1.7941 -0.4245 C 0 0 0 0 0 0 0 0 0 0 0 0 7.2845 0.1614 1.3493 C 0 0 2 0 0 0 0 0 0 0 0 0 8.6469 0.4859 0.9785 N 0 0 0 0 0 0 0 0 0 0 0 0 8.8748 -2.1963 -0.3456 H 0 0 0 0 0 0 0 0 0 0 0 0 7.4064 -3.2974 -0.5776 H 0 0 0 0 0 0 0 0 0 0 0 0 8.1150 -2.4074 -1.9412 H 0 0 0 0 0 0 0 0 0 0 0 0 7.3687 -1.9489 1.2766 H 0 0 0 0 0 0 0 0 0 0 0 0 4.9634 -2.1298 0.4725 H 0 0 0 0 0 0 0 0 0 0 0 0 5.2176 -1.5410 2.1715 H 0 0 0 0 0 0 0 0 0 0 0 0 4.8544 0.0982 -0.3879 H 0 0 0 0 0 0 0 0 0 0 0 0 3.0269 0.1378 -1.0601 H 0 0 0 0 0 0 0 0 0 0 0 0 1.6100 -1.6209 -1.3480 H 0 0 0 0 0 0 0 0 0 0 0 0 2.1775 -2.1389 0.2561 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.1851 -2.0601 0.5544 H 0 0 0 0 0 0 0 0 0 0 0 0 0.4474 -0.5622 1.2634 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.3774 -0.6675 -2.7159 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.4693 -2.1358 -1.7190 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.9261 -1.1779 -2.0226 H 0 0 0 0 0 0 0 0 0 0 0 0 0.8442 0.6426 -1.9736 H 0 0 0 0 0 0 0 0 0 0 0 0 0.1224 2.7932 -2.0225 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.3577 2.8110 -0.2971 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.3212 2.8597 -1.8031 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.8703 1.1843 -2.4119 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.2386 2.2608 0.4132 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.3121 0.4040 1.2179 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.1537 -1.9620 -0.1617 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.5794 -1.4319 1.4644 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.1682 -1.1344 -1.1046 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.5895 -1.7672 0.4998 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.4553 1.1320 2.1751 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.2070 -0.2249 2.3571 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.7128 1.4170 1.9128 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.4099 1.4618 0.0496 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.4439 -1.6613 -1.6489 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.8565 0.0216 1.9382 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.4613 -1.0437 2.2786 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.4644 1.1639 -2.2226 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.8595 -0.5068 -2.2023 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.7214 0.3430 -2.4543 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.3806 1.9879 -2.4702 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.8349 3.3409 -0.3583 H 0 0 0 0 0 0 0 0 0 0 0 0 2.0060 2.0589 -0.4241 H 0 0 0 0 0 0 0 0 0 0 0 0 1.1480 1.3826 0.9780 H 0 0 0 0 0 0 0 0 0 0 0 0 6.7621 2.1860 1.6445 H 0 0 0 0 0 0 0 0 0 0 0 0 5.7135 2.4710 -0.6378 H 0 0 0 0 0 0 0 0 0 0 0 0 6.6745 0.9919 -1.1537 H 0 0 0 0 0 0 0 0 0 0 0 0 7.4843 2.4301 -0.4921 H 0 0 0 0 0 0 0 0 0 0 0 0 7.2752 0.0517 2.4547 H 0 0 0 0 0 0 0 0 0 0 0 0 8.8093 1.5205 1.0439 H 0 0 0 0 0 0 0 0 0 0 0 0 9.3254 -0.0649 1.5359 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 1 0 7 8 1 0 8 9 1 0 9 10 1 0 10 11 1 6 10 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 19 20 1 1 19 21 1 0 21 22 1 0 22 23 2 0 23 24 1 0 24 25 2 0 24 26 1 0 26 27 1 0 21 28 1 0 28 29 1 0 29 30 1 0 30 31 1 1 12 32 1 0 5 33 1 0 33 34 1 0 34 35 1 0 34 36 1 0 36 37 1 0 36 3 1 0 32 7 1 0 16 10 1 0 30 19 1 0 30 15 1 0 27 22 1 0 1 38 1 0 1 39 1 0 1 40 1 0 3 41 1 1 4 42 1 0 4 43 1 0 5 44 1 6 7 45 1 6 8 46 1 0 8 47 1 0 9 48 1 0 9 49 1 0 11 50 1 0 11 51 1 0 11 52 1 0 12 53 1 6 13 54 1 0 13 55 1 0 14 56 1 0 14 57 1 0 15 58 1 1 16 59 1 1 17 60 1 0 17 61 1 0 18 62 1 0 18 63 1 0 20 64 1 0 20 65 1 0 20 66 1 0 21 67 1 1 23 68 1 0 27 69 1 0 27 70 1 0 28 71 1 0 28 72 1 0 29 73 1 0 29 74 1 0 31 75 1 0 32 76 1 0 32 77 1 0 34 78 1 1 35 79 1 0 35 80 1 0 35 81 1 0 36 82 1 1 37 83 1 0 37 84 1 0 M END

Standard InCHIKey	QLCJXHUAXDJDFZ-WMXVCYNISA-N
Standard InCHI	InChI=1S/C30H47NO6/c1-17-27(31)24(34-4)15-26(36-17)37-20-7-10-28(2)19(14-20)5-6-23-22(28)8-11-29(3)21(9-12-30(23,29)33)18-13-25(32)35-16-18/h13,17,19-24,26-27,33H,5-12,14-16,31H2,1-4H3/t17-,19+,20+,21+,22-,23-,24-,26-,27+,28-,29-,30+/m1/s1
SMILES	CO[C@@H]1C[C@@H](O[C@H]2CC[C@]3(C)[C@@H](CC[C@@H]4[C@H]3CC[C@]3(C)[C@H](C5=CC(=O)OC5)CC[C@]43O)C2)O[C@H](C)[C@@H]1N

Calculated Properties

Physi-Chem Properties

Molecular Weight:	517.34	Volume:	534.562 ? Van der Waals volume.
Dense:	0.968	LogP:	2.902 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.181 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.433 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	4.0	Rigid Bonds:	32.0
TPSA:	100.24 ? Topological Polar Surface Area.	H-Bond Acceptor:	7.0
H-Bond Donor:	3.0	Rings:	6.0
Heavy Atoms:	7.0

MedChem Properties

QED Drug-Likeness Score:	0.428	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	5.137	Fsp³:	0.9
MCE-18:	106.667 ? 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:	0.969	Fluc inhibitor:	0.003 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.017 ? 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:	0.024	Promiscuous compounds:	0.248

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.247	MDCK Permeability:	-4.983
Pgp-inhibitor:	0.094	Pgp-substrate:	0.92
PAMPA:	0.922 ? 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):	0.003
20% Bioavailability (F20%):	0.672	30% Bioavailability (F30%):	0.271
50% Bioavailability (F50%):	0.926

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.02	MRP1:	0.92
Plasma Protein Binding (PPB):	89.003%	Volume Distribution (VD):	0.442
Fu:	10.558% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.99
OATP1B3 inhibitor:	0.966	BCRP inhibitor:	0.015
BSEP inhibitor:	0.976

ADMET: Metabolism

CYP1A2-inhibitor:	0.521	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	1.0	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.022	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.001	CYP2D6-substrate:	0.008
CYP3A4-inhibitor:	1.0	CYP3A4-substrate:	0.958
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.011
HLM stability:	0.01 ? 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):

6.977

Half-life (T1/2):

2.015

ADMET: Toxicity

hERG Blockers:	0.289	hERG Blockers (10um):	0.661
Human Hepatotoxicity (H-HT):	0.855	Drug-induced Liver Injury (DILI):	0.908
AMES Toxicity:	0.85	Rat Oral Acute Toxicity:	0.763
Maximum Recommended Daily Dose:	0.984	Skin Sensitization:	1.0
Carcinogencity:	0.945	Eye Corrosion:	0.001
Eye Irritation:	0.026	Respiratory Toxicity:	0.835
Drug-induced Neurotoxicity:	0.262	Ototoxicity:	0.853
Hematotoxicity:	0.803	Drug-induced Nephrotoxicity:	0.992
Genotoxicity:	0.984	RPMI-8226 Immunitoxicity:	0.297
A549 Cytotoxicity:	0.584	Hek293 Cytotoxicity:	0.88
BCF:	1.35 ? 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:	3.798 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.163 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.676 ? 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
NPO30941	Holarrhena antidysenterica	Species	Apocynaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO30941	Holarrhena antidysenterica	Species	Apocynaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO30941	Holarrhena antidysenterica	Species	Apocynaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]

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

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

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 NPC558996 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	11304
0.1-0.2	34843
0.2-0.3	3431
0.3-0.4	60
0.4-0.5	117
0.5-0.6	70
0.6-0.7	19
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	Natural Product ID
0.7531	Intermediate Similarity	NPC84949
0.7531	Intermediate Similarity	NPC480562
0.7531	Intermediate Similarity	NPC74945
0.7531	Intermediate Similarity	NPC31354
0.7531	Intermediate Similarity	NPC69576
0.7273	Intermediate Similarity	NPC246399
0.7273	Intermediate Similarity	NPC34977
0.716	Intermediate Similarity	NPC471633
0.7143	Intermediate Similarity	NPC484202
0.6905	Remote Similarity	NPC199428
0.6905	Remote Similarity	NPC109448
0.6905	Remote Similarity	NPC310341
0.6744	Remote Similarity	NPC93883
0.6591	Remote Similarity	NPC72260
0.6552	Remote Similarity	NPC483822
0.6548	Remote Similarity	NPC99620
0.6522	Remote Similarity	NPC55532
0.6395	Remote Similarity	NPC5311
0.622	Remote Similarity	NPC221196
0.6211	Remote Similarity	NPC486146
0.6207	Remote Similarity	NPC99080
0.617	Remote Similarity	NPC486143
0.617	Remote Similarity	NPC486142
0.617	Remote Similarity	NPC486149
0.6162	Remote Similarity	NPC475419
0.6	Remote Similarity	NPC120390
0.6	Remote Similarity	NPC74259
0.6	Remote Similarity	NPC305574
0.5978	Remote Similarity	NPC103534
0.5978	Remote Similarity	NPC44899
0.5978	Remote Similarity	NPC304260
0.5978	Remote Similarity	NPC29639
0.5941	Remote Similarity	NPC474908
0.5922	Remote Similarity	NPC474423
0.5914	Remote Similarity	NPC30483
0.5914	Remote Similarity	NPC470897
0.5889	Remote Similarity	NPC250556
0.5851	Remote Similarity	NPC236973
0.5851	Remote Similarity	NPC292467
0.58	Remote Similarity	NPC486144
0.58	Remote Similarity	NPC486145
0.58	Remote Similarity	NPC486147
0.58	Remote Similarity	NPC486148
0.5784	Remote Similarity	NPC486134
0.5784	Remote Similarity	NPC486141
0.5778	Remote Similarity	NPC76572
0.5778	Remote Similarity	NPC193382
0.5714	Remote Similarity	NPC329986
0.5714	Remote Similarity	NPC140092
0.5667	Remote Similarity	NPC479356
0.5667	Remote Similarity	NPC469750
0.5667	Remote Similarity	NPC77299
0.5667	Remote Similarity	NPC34390
0.5667	Remote Similarity	NPC480906
0.5667	Remote Similarity	NPC479355
0.5644	Remote Similarity	NPC475590
0.5625	Remote Similarity	NPC268829
0.5625	Remote Similarity	NPC295110
0.5618	Remote Similarity	NPC473852
0.5543	Remote Similarity	NPC180079
0.551	Remote Similarity	NPC486135
0.551	Remote Similarity	NPC486137
0.5495	Remote Similarity	NPC477580
0.5474	Remote Similarity	NPC173555
0.5474	Remote Similarity	NPC5883
0.5435	Remote Similarity	NPC152615
0.5435	Remote Similarity	NPC480914
0.5426	Remote Similarity	NPC193893
0.537	Remote Similarity	NPC286809
0.5347	Remote Similarity	NPC486138
0.5347	Remote Similarity	NPC276838
0.5333	Remote Similarity	NPC474418
0.5312	Remote Similarity	NPC488935
0.5312	Remote Similarity	NPC488936
0.53	Remote Similarity	NPC232785
0.53	Remote Similarity	NPC486139
0.5217	Remote Similarity	NPC196429
0.5208	Remote Similarity	NPC480907
0.5204	Remote Similarity	NPC32177
0.5204	Remote Similarity	NPC469756
0.5204	Remote Similarity	NPC275901
0.52	Remote Similarity	NPC125077
0.5192	Remote Similarity	NPC486136
0.5161	Remote Similarity	NPC486126
0.5152	Remote Similarity	NPC480910
0.5152	Remote Similarity	NPC240070
0.5152	Remote Similarity	NPC480909
0.5119	Remote Similarity	NPC222875
0.5119	Remote Similarity	NPC25177
0.5111	Remote Similarity	NPC39485
0.5109	Remote Similarity	NPC479351
0.5109	Remote Similarity	NPC479352
0.51	Remote Similarity	NPC231518
0.51	Remote Similarity	NPC488944
0.5054	Remote Similarity	NPC486129
0.505	Remote Similarity	NPC208193
0.5047	Remote Similarity	NPC117445
0.5047	Remote Similarity	NPC308262

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC558996 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	5337
0.1-0.2	3711
0.2-0.3	87
0.3-0.4	3
0.4-0.5	3
0.5-0.6	7
0.6-0.7	2
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
0.6591	Remote Similarity	NPD8294	Phase 4
0.6522	Remote Similarity	NPD8377	Phase 4
0.5889	Remote Similarity	NPD7507	Pre-clinical
0.5889	Remote Similarity	NPD8335	Phase 4
0.5652	Remote Similarity	NPD8380	Approved
0.5474	Remote Similarity	NPD8296	Phase 4
0.5455	Remote Similarity	NPD8378	Pre-clinical
0.5455	Remote Similarity	NPD8379	Approved
0.51	Remote Similarity	NPD8033	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