NPASS Compound

Natural Product: NPC505727

Natural Product ID	NPC505727
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	(2~{R},3~{R},4~{S},5~{R},6~{R})-2-[[(3~{S},8~{S},9~{S},10~{R},13~{R},14~{S},17~{R})-10,13-dimethyl-17-[(1~{S})-1-[(2~{S},5~{S})-5-methyl-2-piperidyl]ethyl]-2,3,4,7,8,9,11,12,14,15,16,17-dodecahydro-1~{H}-cyclopenta[a]phenanthren-3-yl]oxy]-6-(hydroxymethyl)tetrahydropyran-3,4,5-triol
IUPAC Name	(2~{R},3~{R},4~{S},5~{R},6~{R})-2-[[(3~{S},8~{S},9~{S},10~{R},13~{R},14~{S},17~{R})-10,13-dimethyl-17-[(1~{S})-1-[(2~{S},5~{S})-5-methyl-2-piperidyl]ethyl]-2,3,4,7,8,9,11,12,14,15,16,17-dodecahydro-1~{H}-cyclopenta[a]phenanthren-3-yl]oxy]-6-(hydroxymethyl)tetrahydropyran-3,4,5-triol
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 95100 0 0 0 0 0 0 0 0999 V2000 -10.2251 0.7975 -1.5304 C 0 0 0 0 0 0 0 0 0 0 0 0 -9.0161 0.1213 -0.9695 C 0 0 1 0 0 0 0 0 0 0 0 0 -7.8181 0.2068 -1.8504 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.5854 -0.4665 -1.2307 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.4870 -0.2255 0.2186 C 0 0 1 0 0 0 0 0 0 0 0 0 -5.1288 0.0761 0.7540 C 0 0 1 0 0 0 0 0 0 0 0 0 -5.2925 0.3588 2.2805 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.1018 -1.0206 0.6769 C 0 0 1 0 0 0 0 0 0 0 0 0 -3.8320 -1.4752 -0.7354 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.6653 -2.4605 -0.4530 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.8469 -1.7287 0.5729 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.6427 -1.1470 -0.1018 C 0 0 2 0 0 0 0 0 0 0 0 0 0.3070 -2.3334 -0.3209 C 0 0 0 0 0 0 0 0 0 0 0 0 1.5578 -1.8567 -0.9009 C 0 0 0 0 0 0 0 0 0 0 0 0 2.0127 -0.6306 -0.6951 C 0 0 0 0 0 0 0 0 0 0 0 0 3.2989 -0.2548 -1.3356 C 0 0 0 0 0 0 0 0 0 0 0 0 4.2457 0.3404 -0.2932 C 0 0 1 0 0 0 0 0 0 0 0 0 5.3790 0.8078 -0.9060 O 0 0 0 0 0 0 0 0 0 0 0 0 6.5427 0.1985 -0.4447 C 0 0 2 0 0 0 0 0 0 0 0 0 7.4518 1.0792 0.0900 O 0 0 0 0 0 0 0 0 0 0 0 0 8.5330 0.3265 0.5653 C 0 0 2 0 0 0 0 0 0 0 0 0 9.3924 1.1131 1.5104 C 0 0 0 0 0 0 0 0 0 0 0 0 9.8935 2.2355 0.8434 O 0 0 0 0 0 0 0 0 0 0 0 0 9.3856 -0.0986 -0.6099 C 0 0 2 0 0 0 0 0 0 0 0 0 10.4308 0.8252 -0.7220 O 0 0 0 0 0 0 0 0 0 0 0 0 8.5423 -0.0358 -1.8492 C 0 0 2 0 0 0 0 0 0 0 0 0 8.4152 1.2625 -2.3113 O 0 0 0 0 0 0 0 0 0 0 0 0 7.1604 -0.5847 -1.5821 C 0 0 1 0 0 0 0 0 0 0 0 0 7.2399 -1.9597 -1.2910 O 0 0 0 0 0 0 0 0 0 0 0 0 3.5588 1.4381 0.4928 C 0 0 0 0 0 0 0 0 0 0 0 0 2.2865 0.9345 1.1287 C 0 0 0 0 0 0 0 0 0 0 0 0 1.3146 0.3872 0.1354 C 0 0 1 0 0 0 0 0 0 0 0 0 0.9141 1.5364 -0.7787 C 0 0 0 0 0 0 0 0 0 0 0 0 0.1119 -0.1979 0.8383 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.8432 0.8346 1.3312 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.2464 0.6552 0.8026 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.7628 -0.7021 1.2182 C 0 0 1 0 0 0 0 0 0 0 0 0 -2.6472 -0.8211 2.7271 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.3488 0.9296 0.5409 N 0 0 0 0 0 0 0 0 0 0 0 0 -8.7382 0.6301 0.4180 C 0 0 0 0 0 0 0 0 0 0 0 0 -10.9154 1.1255 -0.7038 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.9634 1.6654 -2.1580 H 0 0 0 0 0 0 0 0 0 0 0 0 -10.8487 0.0829 -2.1428 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.2571 -0.9757 -0.8464 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.0625 -0.2665 -2.8143 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.5673 1.2487 -2.0458 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.7726 -1.5615 -1.4112 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.7089 -0.1650 -1.8044 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.9729 -1.0709 0.7876 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.6956 0.9911 0.3263 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.1687 -0.5403 2.8806 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.7486 1.2564 2.5845 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.3829 0.6390 2.4482 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.4767 -1.9349 1.2234 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.5035 -0.7033 -1.4246 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.5901 -2.1099 -1.1860 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.1493 -2.7064 -1.3804 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.1080 -3.3566 0.0476 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.5139 -2.4132 1.3962 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.8626 -0.6520 -1.0652 H 0 0 0 0 0 0 0 0 0 0 0 0 0.4782 -2.7517 0.6928 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.1846 -3.0328 -1.0011 H 0 0 0 0 0 0 0 0 0 0 0 0 2.1251 -2.5658 -1.5302 H 0 0 0 0 0 0 0 0 0 0 0 0 3.1964 0.3911 -2.2152 H 0 0 0 0 0 0 0 0 0 0 0 0 3.8468 -1.1714 -1.7089 H 0 0 0 0 0 0 0 0 0 0 0 0 4.5299 -0.4319 0.4347 H 0 0 0 0 0 0 0 0 0 0 0 0 6.2915 -0.5552 0.3478 H 0 0 0 0 0 0 0 0 0 0 0 0 8.1447 -0.5821 1.0961 H 0 0 0 0 0 0 0 0 0 0 0 0 8.8711 1.3756 2.4515 H 0 0 0 0 0 0 0 0 0 0 0 0 10.2899 0.4773 1.7303 H 0 0 0 0 0 0 0 0 0 0 0 0 10.3500 2.7973 1.5242 H 0 0 0 0 0 0 0 0 0 0 0 0 9.7998 -1.1209 -0.4379 H 0 0 0 0 0 0 0 0 0 0 0 0 11.2077 0.5061 -0.1656 H 0 0 0 0 0 0 0 0 0 0 0 0 9.0731 -0.6109 -2.6371 H 0 0 0 0 0 0 0 0 0 0 0 0 9.1602 1.8502 -2.0216 H 0 0 0 0 0 0 0 0 0 0 0 0 6.5855 -0.4437 -2.5319 H 0 0 0 0 0 0 0 0 0 0 0 0 8.1080 -2.2655 -1.6244 H 0 0 0 0 0 0 0 0 0 0 0 0 3.4113 2.3640 -0.1041 H 0 0 0 0 0 0 0 0 0 0 0 0 4.2456 1.7107 1.3220 H 0 0 0 0 0 0 0 0 0 0 0 0 1.8834 1.7629 1.7395 H 0 0 0 0 0 0 0 0 0 0 0 0 2.5743 0.1178 1.8232 H 0 0 0 0 0 0 0 0 0 0 0 0 1.6561 1.5694 -1.6027 H 0 0 0 0 0 0 0 0 0 0 0 0 1.0097 2.5160 -0.2556 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.0695 1.3864 -1.2355 H 0 0 0 0 0 0 0 0 0 0 0 0 0.4685 -0.8412 1.6695 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.4917 1.8258 0.9509 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.8362 0.9179 2.4404 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.1900 0.6849 -0.3046 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.8448 1.4957 1.1846 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.9250 0.0772 3.2762 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.2020 -1.6869 3.1247 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.5333 -0.9421 2.9958 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.1014 1.6820 -0.1315 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.1141 -0.0582 1.2053 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.2921 1.5765 0.5533 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 6 8 1 0 8 9 1 0 9 10 1 0 10 11 1 0 11 12 1 0 12 13 1 0 13 14 1 0 14 15 2 0 15 16 1 0 16 17 1 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 21 24 1 0 24 25 1 0 24 26 1 0 26 27 1 0 26 28 1 0 28 29 1 0 17 30 1 0 30 31 1 0 31 32 1 0 32 33 1 6 32 34 1 0 34 35 1 0 35 36 1 0 36 37 1 0 37 38 1 1 5 39 1 0 39 40 1 0 40 2 1 0 37 8 1 0 37 11 1 0 34 12 1 0 32 15 1 0 28 19 1 0 1 41 1 0 1 42 1 0 1 43 1 0 2 44 1 1 3 45 1 0 3 46 1 0 4 47 1 0 4 48 1 0 5 49 1 1 6 50 1 6 7 51 1 0 7 52 1 0 7 53 1 0 8 54 1 1 9 55 1 0 9 56 1 0 10 57 1 0 10 58 1 0 11 59 1 1 12 60 1 6 13 61 1 0 13 62 1 0 14 63 1 0 16 64 1 0 16 65 1 0 17 66 1 1 19 67 1 1 21 68 1 1 22 69 1 0 22 70 1 0 23 71 1 0 24 72 1 1 25 73 1 0 26 74 1 6 27 75 1 0 28 76 1 6 29 77 1 0 30 78 1 0 30 79 1 0 31 80 1 0 31 81 1 0 33 82 1 0 33 83 1 0 33 84 1 0 34 85 1 1 35 86 1 0 35 87 1 0 36 88 1 0 36 89 1 0 38 90 1 0 38 91 1 0 38 92 1 0 39 93 1 0 40 94 1 0 40 95 1 0 M END

Standard InCHIKey	SEQLYLLGDOFFKK-JZDVVXAISA-N
Standard InCHI	InChI=1S/C33H55NO6/c1-18-5-10-26(34-16-18)19(2)23-8-9-24-22-7-6-20-15-21(11-13-32(20,3)25(22)12-14-33(23,24)4)39-31-30(38)29(37)28(36)27(17-35)40-31/h6,18-19,21-31,34-38H,5,7-17H2,1-4H3/t18-,19-,21-,22-,23+,24-,25-,26-,27+,28-,29-,30+,31+,32-,33-/m0/s1
SMILES	C[C@H]1CC[C@@H]([C@@H](C)[C@H]2CC[C@H]3[C@@H]4CC=C5C[C@@H](O[C@@H]6O[C@H](CO)[C@H](O)[C@H](O)[C@H]6O)CC[C@]5(C)[C@H]4CC[C@@]23C)NC1

Calculated Properties

Physi-Chem Properties

Molecular Weight:	561.4	Volume:	589.087 ? Van der Waals volume.
Dense:	0.953	LogP:	4.513 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	4.401 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-5.183 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	5.0	Rigid Bonds:	32.0
TPSA:	111.41 ? Topological Polar Surface Area.	H-Bond Acceptor:	7.0
H-Bond Donor:	5.0	Rings:	6.0
Heavy Atoms:	7.0

MedChem Properties

QED Drug-Likeness Score:	0.325	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	5.192	Fsp³:	0.939
MCE-18:	105.688 ? 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:	0.904	Fluc inhibitor:	0.0 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.007 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.0 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.004	Promiscuous compounds:	0.007

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.811	MDCK Permeability:	-5.125
Pgp-inhibitor:	0.0	Pgp-substrate:	0.029
PAMPA:	0.866 ? 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%):	0.004	30% Bioavailability (F30%):	0.883
50% Bioavailability (F50%):	0.997

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.0	MRP1:	0.017
Plasma Protein Binding (PPB):	70.077%	Volume Distribution (VD):	-0.249
Fu:	29.015% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.999
OATP1B3 inhibitor:	0.985	BCRP inhibitor:	0.005
BSEP inhibitor:	0.0

ADMET: Metabolism

CYP1A2-inhibitor:	0.006	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.849	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.0	CYP2C9-substrate:	0.004
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.183
CYP3A4-inhibitor:	0.859	CYP3A4-substrate:	1.0
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.984
HLM stability:	0.445 ? 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):

4.737

Half-life (T1/2):

0.897

ADMET: Toxicity

hERG Blockers:	0.037	hERG Blockers (10um):	0.066
Human Hepatotoxicity (H-HT):	0.578	Drug-induced Liver Injury (DILI):	0.825
AMES Toxicity:	0.886	Rat Oral Acute Toxicity:	0.073
Maximum Recommended Daily Dose:	0.058	Skin Sensitization:	1.0
Carcinogencity:	0.627	Eye Corrosion:	0.007
Eye Irritation:	0.348	Respiratory Toxicity:	0.82
Drug-induced Neurotoxicity:	0.007	Ototoxicity:	0.963
Hematotoxicity:	0.934	Drug-induced Nephrotoxicity:	0.956
Genotoxicity:	0.006	RPMI-8226 Immunitoxicity:	0.14
A549 Cytotoxicity:	0.989	Hek293 Cytotoxicity:	0.762
BCF:	2.423 ? 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:	4.03 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.995 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.694 ? 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
NPO50010	Veratrum taliense	Species	Melanthiaceae	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

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 NPC505727 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	20213
0.1-0.2	24406
0.2-0.3	4175
0.3-0.4	924
0.4-0.5	100
0.5-0.6	31
0.6-0.7	5
0.7-0.8	0
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
0.84	Intermediate Similarity	NPC296686
0.6974	Remote Similarity	NPC22140
0.6974	Remote Similarity	NPC243728
0.6974	Remote Similarity	NPC158088
0.6375	Remote Similarity	NPC282669
0.6301	Remote Similarity	NPC474164
0.5909	Remote Similarity	NPC181845
0.5897	Remote Similarity	NPC207617
0.5897	Remote Similarity	NPC607440
0.5843	Remote Similarity	NPC272015
0.5806	Remote Similarity	NPC600456
0.57	Remote Similarity	NPC150057
0.57	Remote Similarity	NPC147753
0.5699	Remote Similarity	NPC297058
0.5684	Remote Similarity	NPC15249
0.5684	Remote Similarity	NPC25455
0.5682	Remote Similarity	NPC486114
0.5488	Remote Similarity	NPC473890
0.5467	Remote Similarity	NPC12035
0.5357	Remote Similarity	NPC21064
0.5294	Remote Similarity	NPC470434
0.5258	Remote Similarity	NPC295980
0.5222	Remote Similarity	NPC242748
0.5196	Remote Similarity	NPC122819
0.5196	Remote Similarity	NPC477809
0.5161	Remote Similarity	NPC295389
0.5158	Remote Similarity	NPC86020
0.5109	Remote Similarity	NPC318135
0.51	Remote Similarity	NPC305423
0.51	Remote Similarity	NPC113044
0.51	Remote Similarity	NPC283829
0.51	Remote Similarity	NPC161676
0.5062	Remote Similarity	NPC176012
0.5059	Remote Similarity	NPC154452
0.5059	Remote Similarity	NPC121072
0.5057	Remote Similarity	NPC608180
0.5051	Remote Similarity	NPC94272

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC505727 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	6635
0.1-0.2	2345
0.2-0.3	151
0.3-0.4	14
0.4-0.5	3
0.5-0.6	2
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
0.57	Remote Similarity	NPD8450	Suspended
0.5196	Remote Similarity	NPD8449	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