NPASS Compound

Natural Product: NPC471633

Natural Product ID	NPC471633
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	4-[3-(4,5-Dihydroxy-6-Methyl-Tetrahydro-Pyran-2-Yloxy)-14-Hydroxy-10,13-Dimethyl-Hexadecahydro-Cyclopenta[A]Phenanthren-17-Yl]-5H-Furan-2-One
IUPAC Name	3-[(3S,5S,8R,9S,10S,13R,14R,17R)-3-[(2R,4S,5S,6S)-4,5-dihydroxy-6-methyloxan-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]-2H-furan-5-one
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL3085490
PubChem CID	76335204
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0000258] Steroids and steroid derivatives [CHEMONTID:0001125] Steroid lactones [CHEMONTID:0001555] Cardenolides and derivatives [CHEMONTID:0001559] Cardenolide glycosides 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 80 85 0 0 0 0 0 0 0 0999 V2000 7.9901 -0.9880 -0.8844 C 0 0 0 0 0 0 0 0 0 0 0 0 7.2195 -1.0590 0.4148 C 0 0 0 0 0 0 0 0 0 0 0 0 7.6169 0.0772 1.3121 C 0 0 0 0 0 0 0 0 0 0 0 0 6.5753 1.1765 1.3254 C 0 0 0 0 0 0 0 0 0 0 0 0 6.0146 1.2038 -0.0843 C 0 0 0 0 0 0 0 0 0 0 0 0 5.2015 -0.0495 -0.2504 C 0 0 0 0 0 0 0 0 0 0 0 0 5.8939 -1.1422 0.1340 O 0 0 0 0 0 0 0 0 0 0 0 0 3.9981 -0.0002 0.4366 O 0 0 0 0 0 0 0 0 0 0 0 0 2.8879 -0.0814 -0.3891 C 0 0 0 0 0 0 0 0 0 0 0 0 2.1275 -1.3597 -0.1834 C 0 0 0 0 0 0 0 0 0 0 0 0 1.0516 -1.2627 0.8327 C 0 0 0 0 0 0 0 0 0 0 0 0 0.1545 -0.0666 0.6519 C 0 0 0 0 0 0 0 0 0 0 0 0 0.6033 0.6913 -0.5519 C 0 0 0 0 0 0 0 0 0 0 0 0 2.0458 1.1546 -0.3860 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.3398 1.8133 -0.9066 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.6511 1.2110 -1.3481 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.8008 -0.2080 -0.9362 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.3001 -0.4486 0.4797 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.2200 0.3251 1.3683 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.6054 -0.2402 1.3147 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.1524 -0.5274 -0.0300 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.1582 -0.8029 -1.0921 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.8521 -0.4059 -2.3528 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.9781 0.5403 -1.9771 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.0708 0.5886 -0.4953 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.4585 0.4526 -0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.5773 0.3349 -0.6941 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.7210 0.2271 0.2177 C 0 0 0 0 0 0 0 0 0 0 0 0 -9.9445 0.1017 -0.0399 O 0 0 0 0 0 0 0 0 0 0 0 0 -8.2125 0.2891 1.5042 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.8163 0.4281 1.4394 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.9656 -2.2073 -1.1610 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.0553 -1.7625 0.0990 C 0 0 0 0 0 0 0 0 0 0 0 0 0.2305 0.7559 1.9210 C 0 0 0 0 0 0 0 0 0 0 0 0 5.5320 0.8652 2.1954 O 0 0 0 0 0 0 0 0 0 0 0 0 7.8865 -0.3045 2.6219 O 0 0 0 0 0 0 0 0 0 0 0 0 7.2944 -0.9184 -1.7701 H 0 0 0 0 0 0 0 0 0 0 0 0 8.7655 -0.1959 -0.8895 H 0 0 0 0 0 0 0 0 0 0 0 0 8.5661 -1.9350 -1.0917 H 0 0 0 0 0 0 0 0 0 0 0 0 7.5198 -1.9967 0.9355 H 0 0 0 0 0 0 0 0 0 0 0 0 8.5425 0.5249 0.9038 H 0 0 0 0 0 0 0 0 0 0 0 0 6.9656 2.1564 1.6023 H 0 0 0 0 0 0 0 0 0 0 0 0 5.4230 2.1252 -0.2691 H 0 0 0 0 0 0 0 0 0 0 0 0 6.8414 1.2311 -0.8120 H 0 0 0 0 0 0 0 0 0 0 0 0 5.0309 -0.1432 -1.3607 H 0 0 0 0 0 0 0 0 0 0 0 0 3.3228 -0.1654 -1.4339 H 0 0 0 0 0 0 0 0 0 0 0 0 2.7990 -2.2048 0.0959 H 0 0 0 0 0 0 0 0 0 0 0 0 1.6946 -1.6576 -1.1757 H 0 0 0 0 0 0 0 0 0 0 0 0 1.5227 -1.2760 1.8422 H 0 0 0 0 0 0 0 0 0 0 0 0 0.3751 -2.1567 0.8087 H 0 0 0 0 0 0 0 0 0 0 0 0 0.6491 0.0213 -1.4333 H 0 0 0 0 0 0 0 0 0 0 0 0 2.1962 1.8093 0.4864 H 0 0 0 0 0 0 0 0 0 0 0 0 2.2702 1.7695 -1.2784 H 0 0 0 0 0 0 0 0 0 0 0 0 0.1412 2.4075 -1.7034 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.4376 2.4940 -0.0376 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.6425 1.2797 -2.4750 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.4522 1.8880 -1.0211 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.1305 -0.8319 -1.5994 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.3919 -1.5146 0.7068 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.2797 1.4034 1.0334 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.9376 0.3430 2.4382 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.2604 0.5427 1.8059 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.6540 -1.1104 1.9996 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.1507 0.0582 -3.0696 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.2559 -1.3013 -2.9070 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.7752 1.5296 -2.4413 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.8842 0.1611 -2.4630 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.7184 1.5800 -0.0740 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.7300 0.3122 -1.7638 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.5020 1.3848 1.8798 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.4081 -0.4656 1.9795 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.0541 -2.4752 -0.9649 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.0014 -2.2033 1.1140 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.7486 -2.5762 -0.5942 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.1029 -1.5577 -0.1265 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.4486 1.6159 1.9035 H 0 0 0 0 0 0 0 0 0 0 0 0 1.2456 1.1420 2.1414 H 0 0 0 0 0 0 0 0 0 0 0 0 0.0330 0.0346 2.7640 H 0 0 0 0 0 0 0 0 0 0 0 0 5.7729 0.1482 2.8329 H 0 0 0 0 0 0 0 0 0 0 0 0 8.8450 -0.5963 2.6709 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 13 15 1 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 23 24 1 0 24 25 1 0 25 26 1 0 26 27 2 0 27 28 1 0 28 29 2 0 28 30 1 0 30 31 1 0 22 32 1 0 21 33 1 0 12 34 1 0 4 35 1 0 3 36 1 0 7 2 1 0 14 9 1 0 18 12 1 0 22 17 1 0 25 21 1 0 31 26 1 0 1 37 1 0 1 38 1 0 1 39 1 0 2 40 1 0 3 41 1 0 4 42 1 0 5 43 1 0 5 44 1 0 6 45 1 0 9 46 1 0 10 47 1 0 10 48 1 0 11 49 1 0 11 50 1 0 13 51 1 0 14 52 1 0 14 53 1 0 15 54 1 0 15 55 1 0 16 56 1 0 16 57 1 0 17 58 1 0 18 59 1 0 19 60 1 0 19 61 1 0 20 62 1 0 20 63 1 0 23 64 1 0 23 65 1 0 24 66 1 0 24 67 1 0 25 68 1 0 27 69 1 0 31 70 1 0 31 71 1 0 32 72 1 0 33 73 1 0 33 74 1 0 33 75 1 0 34 76 1 0 34 77 1 0 34 78 1 0 35 79 1 0 36 80 1 0 M END

Standard InCHIKey	NQOMDNMTNVQXRR-SVWWHTAMSA-N
Standard InCHI	InChI=1S/C29H44O7/c1-16-26(32)23(30)14-25(35-16)36-19-6-9-27(2)18(13-19)4-5-22-21(27)7-10-28(3)20(8-11-29(22,28)33)17-12-24(31)34-15-17/h12,16,18-23,25-26,30,32-33H,4-11,13-15H2,1-3H3/t16-,18-,19-,20+,21-,22+,23-,25-,26+,27-,28+,29+/m0/s1
SMILES	CC1C(C(CC(O1)OC2CCC3(C(C2)CCC4C3CCC5(C4(CCC5C6=CC(=O)OC6)O)C)C)O)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	504.31	Volume:	515.06 ? Van der Waals volume.
Dense:	0.979	LogP:	1.929 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.621 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.315 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	3.0	Rigid Bonds:	32.0
TPSA:	105.45 ? 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:	0.399	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	5.027	Fsp³:	0.897
MCE-18:	107.782 ? 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:	0.045	Fluc inhibitor:	0.0 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.019 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.033 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.091	Promiscuous compounds:	0.023

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.578	MDCK Permeability:	-5.143
Pgp-inhibitor:	0.002	Pgp-substrate:	0.02
PAMPA:	0.421 ? 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):	0.012
20% Bioavailability (F20%):	0.001	30% Bioavailability (F30%):	0.007
50% Bioavailability (F50%):	0.231

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.481	MRP1:	0.996
Plasma Protein Binding (PPB):	91.293%	Volume Distribution (VD):	0.087
Fu:	10.219% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.001
OATP1B3 inhibitor:	0.411	BCRP inhibitor:	0.0
BSEP inhibitor:	0.888

ADMET: Metabolism

CYP1A2-inhibitor:	0.006	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.619	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.78	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.016	CYP2D6-substrate:	0.0
CYP3A4-inhibitor:	0.026	CYP3A4-substrate:	0.0
CYP2B6-substrate:	0.892	CYP2C8-inhibitor:	0.0
HLM stability:	0.004 ? 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):

10.031

Half-life (T1/2):

3.178

ADMET: Toxicity

hERG Blockers:	0.345	hERG Blockers (10um):	0.766
Human Hepatotoxicity (H-HT):	0.812	Drug-induced Liver Injury (DILI):	0.329
AMES Toxicity:	0.784	Rat Oral Acute Toxicity:	0.876
Maximum Recommended Daily Dose:	0.994	Skin Sensitization:	0.639
Carcinogencity:	0.655	Eye Corrosion:	0.0
Eye Irritation:	0.0	Respiratory Toxicity:	0.768
Drug-induced Neurotoxicity:	0.153	Ototoxicity:	0.956
Hematotoxicity:	0.135	Drug-induced Nephrotoxicity:	0.134
Genotoxicity:	0.379	RPMI-8226 Immunitoxicity:	0.403
A549 Cytotoxicity:	0.379	Hek293 Cytotoxicity:	0.907
BCF:	1.364 ? 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:	4.293 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.886 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.932 ? 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
NPO32604	asclepias fructicosa	Species	Apocynaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[3981544]

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	1
Relative ionotropic activity	1

Activity Type	# Activity
Others	1
Organism	1

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
NPT2	Others	Unspecified	n.a.	IC50	=	7.04	nM	PMID[24484240]

In vivo activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT938	Organism	Cavia porcellus	Cavia porcellus	Relative ionotropic activity	=	15.0	n.a.	PMID[3981544]

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 NPC471633 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	13180
0.1-0.2	30819
0.2-0.3	5511
0.3-0.4	109
0.4-0.5	77
0.5-0.6	85
0.6-0.7	53
0.7-0.8	2
0.8-0.85	1
0.85-0.9	0
0.9-0.95	1
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.9054	High Similarity	NPC72260
0.8108	Intermediate Similarity	NPC99620
0.7867	Intermediate Similarity	NPC473852
0.7792	Intermediate Similarity	NPC84949
0.7792	Intermediate Similarity	NPC480562
0.7792	Intermediate Similarity	NPC74945
0.7792	Intermediate Similarity	NPC31354
0.7792	Intermediate Similarity	NPC69576
0.7531	Intermediate Similarity	NPC173555
0.75	Intermediate Similarity	NPC474418
0.75	Intermediate Similarity	NPC193893
0.7436	Intermediate Similarity	NPC5311
0.716	Intermediate Similarity	NPC484202
0.716	Intermediate Similarity	NPC93883
0.7125	Intermediate Similarity	NPC199428
0.7125	Intermediate Similarity	NPC109448
0.7125	Intermediate Similarity	NPC310341
0.7093	Intermediate Similarity	NPC55532
0.7	Intermediate Similarity	NPC469750
0.6914	Remote Similarity	NPC76572
0.6914	Remote Similarity	NPC193382
0.6848	Remote Similarity	NPC120390
0.6848	Remote Similarity	NPC74259
0.6824	Remote Similarity	NPC30483
0.6824	Remote Similarity	NPC470897
0.6813	Remote Similarity	NPC475590
0.6744	Remote Similarity	NPC236973
0.6744	Remote Similarity	NPC292467
0.6705	Remote Similarity	NPC486143
0.6705	Remote Similarity	NPC486142
0.6705	Remote Similarity	NPC486149
0.6556	Remote Similarity	NPC486146
0.6548	Remote Similarity	NPC483822
0.6463	Remote Similarity	NPC196429
0.6463	Remote Similarity	NPC484211
0.6421	Remote Similarity	NPC474908
0.6386	Remote Similarity	NPC77299
0.6386	Remote Similarity	NPC480906
0.6386	Remote Similarity	NPC99080
0.6333	Remote Similarity	NPC125077
0.6316	Remote Similarity	NPC475419
0.631	Remote Similarity	NPC480914
0.6292	Remote Similarity	NPC240070
0.6277	Remote Similarity	NPC486144
0.6277	Remote Similarity	NPC486145
0.6277	Remote Similarity	NPC486147
0.6277	Remote Similarity	NPC486148
0.6224	Remote Similarity	NPC474423
0.6216	Remote Similarity	NPC268829
0.6216	Remote Similarity	NPC295110
0.619	Remote Similarity	NPC480915
0.6154	Remote Similarity	NPC208193
0.6145	Remote Similarity	NPC99728
0.6145	Remote Similarity	NPC87250
0.6145	Remote Similarity	NPC244402
0.6145	Remote Similarity	NPC50305
0.6136	Remote Similarity	NPC103534
0.6136	Remote Similarity	NPC44899
0.6136	Remote Similarity	NPC304260
0.6136	Remote Similarity	NPC29639
0.6082	Remote Similarity	NPC486134
0.6082	Remote Similarity	NPC486141
0.6047	Remote Similarity	NPC250556
0.6023	Remote Similarity	NPC480907
0.6	Remote Similarity	NPC157376
0.6	Remote Similarity	NPC17896
0.6	Remote Similarity	NPC469755
0.6	Remote Similarity	NPC284406
0.6	Remote Similarity	NPC197707
0.6	Remote Similarity	NPC251866
0.6	Remote Similarity	NPC142066
0.6	Remote Similarity	NPC603972
0.5977	Remote Similarity	NPC179412
0.5977	Remote Similarity	NPC471356
0.5977	Remote Similarity	NPC471353
0.5977	Remote Similarity	NPC305574
0.5895	Remote Similarity	NPC475219
0.5851	Remote Similarity	NPC329986
0.5851	Remote Similarity	NPC140092
0.5824	Remote Similarity	NPC32177
0.5824	Remote Similarity	NPC469756
0.5824	Remote Similarity	NPC275901
0.5814	Remote Similarity	NPC479356
0.5814	Remote Similarity	NPC34390
0.5814	Remote Similarity	NPC479355
0.5814	Remote Similarity	NPC484210
0.5806	Remote Similarity	NPC486135
0.5806	Remote Similarity	NPC486137
0.5761	Remote Similarity	NPC188234
0.5761	Remote Similarity	NPC480910
0.5761	Remote Similarity	NPC480909
0.5758	Remote Similarity	NPC117445
0.5758	Remote Similarity	NPC308262
0.5745	Remote Similarity	NPC232785
0.5745	Remote Similarity	NPC486139
0.5682	Remote Similarity	NPC180079
0.5632	Remote Similarity	NPC477580
0.5631	Remote Similarity	NPC286809
0.5625	Remote Similarity	NPC486138
0.5625	Remote Similarity	NPC276838
0.5604	Remote Similarity	NPC488935
0.5604	Remote Similarity	NPC5883
0.5604	Remote Similarity	NPC488936
0.5591	Remote Similarity	NPC475556
0.5591	Remote Similarity	NPC311706
0.5568	Remote Similarity	NPC152615
0.5568	Remote Similarity	NPC10823
0.5532	Remote Similarity	NPC231518
0.5532	Remote Similarity	NPC488944
0.5517	Remote Similarity	NPC84987
0.5513	Remote Similarity	NPC196931
0.5513	Remote Similarity	NPC480913
0.5455	Remote Similarity	NPC486136
0.5444	Remote Similarity	NPC277374
0.5443	Remote Similarity	NPC222875
0.5443	Remote Similarity	NPC25177
0.5385	Remote Similarity	NPC187302
0.5354	Remote Similarity	NPC488943
0.5354	Remote Similarity	NPC488942
0.5341	Remote Similarity	NPC309034
0.5333	Remote Similarity	NPC77319
0.5333	Remote Similarity	NPC471351
0.5333	Remote Similarity	NPC471355
0.5319	Remote Similarity	NPC27363
0.5287	Remote Similarity	NPC158344
0.5281	Remote Similarity	NPC6108
0.5281	Remote Similarity	NPC89514
0.5263	Remote Similarity	NPC608063
0.5243	Remote Similarity	NPC486150
0.52	Remote Similarity	NPC479360
0.52	Remote Similarity	NPC479359
0.52	Remote Similarity	NPC488938
0.52	Remote Similarity	NPC488937
0.5172	Remote Similarity	NPC481205
0.5169	Remote Similarity	NPC219085
0.5169	Remote Similarity	NPC486129
0.5165	Remote Similarity	NPC88668
0.5149	Remote Similarity	NPC329636
0.5125	Remote Similarity	NPC189588
0.5111	Remote Similarity	NPC486126
0.5109	Remote Similarity	NPC9499
0.5109	Remote Similarity	NPC471360
0.5109	Remote Similarity	NPC469751
0.5109	Remote Similarity	NPC471361
0.5109	Remote Similarity	NPC86159
0.5109	Remote Similarity	NPC469752
0.5109	Remote Similarity	NPC469754
0.5109	Remote Similarity	NPC70542
0.5063	Remote Similarity	NPC97487
0.5056	Remote Similarity	NPC479351
0.5056	Remote Similarity	NPC479352
0.5054	Remote Similarity	NPC471354
0.5054	Remote Similarity	NPC27507
0.5052	Remote Similarity	NPC475629
0.5051	Remote Similarity	NPC146857
0.5048	Remote Similarity	NPC488945
0.5048	Remote Similarity	NPC488946

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC471633 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	5748
0.1-0.2	3241
0.2-0.3	145
0.3-0.4	1
0.4-0.5	5
0.5-0.6	1
0.6-0.7	6
0.7-0.8	2
0.8-0.85	0
0.85-0.9	0
0.9-0.95	1
0.95-1	0

Similarity Score	Similarity Level	Drug ID	Developmental Stage
0.9054	High Similarity	NPD8294	Phase 4
0.7531	Intermediate Similarity	NPD8296	Phase 4
0.75	Intermediate Similarity	NPD8377	Phase 4
0.6548	Remote Similarity	NPD8380	Approved
0.6429	Remote Similarity	NPD8335	Phase 4
0.6264	Remote Similarity	NPD8378	Pre-clinical
0.6264	Remote Similarity	NPD8379	Approved
0.6047	Remote Similarity	NPD7507	Pre-clinical
0.6	Remote Similarity	NPD7319	Approved
0.5532	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