NPASS Compound

Natural Product: NPC131665

Natural Product ID	NPC131665
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	(20R,23R)-3Beta,20-Dihydroxyldammarane-24-Ene-21-Oic Acid-21,23-Lactone
IUPAC Name	(3R,5R)-3-hydroxy-3-[(3S,5R,8R,9R,10R,13R,14R,17S)-3-hydroxy-4,4,8,10,14-pentamethyl-2,3,5,6,7,9,11,12,13,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-17-yl]-5-(2-methylprop-1-enyl)oxolan-2-one
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL2313419
PubChem CID	71717335
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0000259] Prenol lipids [CHEMONTID:0001553] Triterpenoids

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 82 86 0 0 0 0 0 0 0 0999 V2000 9.0066 0.0700 -0.6623 C 0 0 0 0 0 0 0 0 0 0 0 0 7.5348 -0.1679 -0.5228 C 0 0 0 0 0 0 0 0 0 0 0 0 7.1122 -1.1319 0.2389 C 0 0 0 0 0 0 0 0 0 0 0 0 5.7150 -1.4648 0.4575 C 0 0 1 0 0 0 0 0 0 0 0 0 4.8601 -0.4260 1.1015 C 0 0 0 0 0 0 0 0 0 0 0 0 3.4676 -0.9970 0.8392 C 0 0 1 0 0 0 0 0 0 0 0 0 2.4508 0.0981 0.7024 C 0 0 1 0 0 0 0 0 0 0 0 0 2.7072 1.0090 -0.4856 C 0 0 0 0 0 0 0 0 0 0 0 0 1.3312 1.2488 -1.1255 C 0 0 0 0 0 0 0 0 0 0 0 0 0.3901 0.7815 -0.1002 C 0 0 2 0 0 0 0 0 0 0 0 0 0.2417 1.8675 0.9384 C 0 0 0 0 0 0 0 0 0 0 0 0 1.1003 -0.4461 0.4789 C 0 0 2 0 0 0 0 0 0 0 0 0 0.3820 -0.9541 1.6807 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.0705 -1.1626 1.4308 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7277 -0.0600 0.6594 C 0 0 2 0 0 0 0 0 0 0 0 0 -3.1810 -0.2755 0.4530 C 0 0 1 0 0 0 0 0 0 0 0 0 -3.5539 -1.6823 0.1348 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.8671 0.0268 1.8016 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.3540 -0.1762 1.7159 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.0334 0.4663 0.5804 C 0 0 1 0 0 0 0 0 0 0 0 0 -5.2448 0.6478 -0.6738 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.6420 -0.3332 -1.7325 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.6482 2.0374 -1.2182 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.7676 0.7634 -0.4521 C 0 0 2 0 0 0 0 0 0 0 0 0 -3.0450 0.9612 -1.7412 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.5981 1.3078 -1.4354 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.9361 0.2594 -0.5926 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.7167 -0.9487 -1.4616 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.1544 -0.3319 0.2422 O 0 0 0 0 0 0 0 0 0 0 0 0 3.6261 -1.8807 -0.3094 C 0 0 0 0 0 0 0 0 0 0 0 0 2.7604 -2.6181 -0.8381 O 0 0 0 0 0 0 0 0 0 0 0 0 4.9754 -1.7563 -0.7358 O 0 0 0 0 0 0 0 0 0 0 0 0 3.1834 -1.8100 1.9496 O 0 0 0 0 0 0 0 0 0 0 0 0 6.6247 0.7195 -1.2691 C 0 0 0 0 0 0 0 0 0 0 0 0 9.1993 0.4571 -1.6764 H 0 0 0 0 0 0 0 0 0 0 0 0 9.5544 -0.8831 -0.5572 H 0 0 0 0 0 0 0 0 0 0 0 0 9.3712 0.7789 0.0970 H 0 0 0 0 0 0 0 0 0 0 0 0 7.8482 -1.7630 0.7744 H 0 0 0 0 0 0 0 0 0 0 0 0 5.6202 -2.4104 1.0788 H 0 0 0 0 0 0 0 0 0 0 0 0 5.0849 -0.4336 2.1927 H 0 0 0 0 0 0 0 0 0 0 0 0 4.9660 0.5916 0.7460 H 0 0 0 0 0 0 0 0 0 0 0 0 2.5057 0.7100 1.6496 H 0 0 0 0 0 0 0 0 0 0 0 0 3.3024 0.4907 -1.2701 H 0 0 0 0 0 0 0 0 0 0 0 0 3.1771 1.9596 -0.2179 H 0 0 0 0 0 0 0 0 0 0 0 0 1.2506 0.8390 -2.1235 H 0 0 0 0 0 0 0 0 0 0 0 0 1.1847 2.3648 -1.2423 H 0 0 0 0 0 0 0 0 0 0 0 0 0.1778 1.5136 1.9652 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.6088 2.5309 0.7466 H 0 0 0 0 0 0 0 0 0 0 0 0 1.1510 2.5402 0.9087 H 0 0 0 0 0 0 0 0 0 0 0 0 1.0969 -1.2177 -0.2796 H 0 0 0 0 0 0 0 0 0 0 0 0 0.5976 -0.3666 2.6180 H 0 0 0 0 0 0 0 0 0 0 0 0 0.8255 -1.9691 1.9136 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.2271 -2.1712 1.0119 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.5604 -1.2000 2.4495 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.6351 0.8639 1.3069 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.1017 -2.1144 -0.7494 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.2579 -2.3013 1.0342 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.6405 -1.7973 0.0662 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.4906 -0.5898 2.6107 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.7013 1.1227 1.9554 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.7553 0.2234 2.6974 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.5511 -1.2862 1.8118 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.5018 1.4267 0.9522 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.1546 0.1457 -2.6195 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.8343 -0.9287 -2.1547 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.4158 -1.0742 -1.3710 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.5587 2.0528 -2.3227 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.7091 2.2138 -0.9585 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.0470 2.8323 -0.7308 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.6321 1.7463 0.1030 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.4738 1.9034 -2.1994 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.1661 0.1869 -2.4896 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.0743 1.2857 -2.4363 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.5140 2.3264 -1.0675 H 0 0 0 0 0 0 0 0 0 0 0 0 0.1974 -0.8985 -2.0749 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.5539 -1.0247 -2.2184 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.7086 -1.9022 -0.9357 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.7100 -0.5296 1.0114 H 0 0 0 0 0 0 0 0 0 0 0 0 3.2742 -2.7671 1.7506 H 0 0 0 0 0 0 0 0 0 0 0 0 7.1082 0.9362 -2.2733 H 0 0 0 0 0 0 0 0 0 0 0 0 6.5097 1.6705 -0.7005 H 0 0 0 0 0 0 0 0 0 0 0 0 5.6516 0.2741 -1.5249 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 2 3 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 1 10 12 1 0 12 13 1 0 13 14 1 0 14 15 1 0 15 16 1 0 16 17 1 6 16 18 1 0 18 19 1 0 19 20 1 0 20 21 1 0 21 22 1 0 21 23 1 0 21 24 1 0 24 25 1 0 25 26 1 0 26 27 1 0 27 28 1 6 20 29 1 0 6 30 1 0 30 31 2 0 30 32 1 0 6 33 1 1 2 34 1 0 32 4 1 0 12 7 1 0 27 15 1 0 27 10 1 0 24 16 1 0 1 35 1 0 1 36 1 0 1 37 1 0 3 38 1 0 4 39 1 1 5 40 1 0 5 41 1 0 7 42 1 1 8 43 1 0 8 44 1 0 9 45 1 0 9 46 1 0 11 47 1 0 11 48 1 0 11 49 1 0 12 50 1 6 13 51 1 0 13 52 1 0 14 53 1 0 14 54 1 0 15 55 1 1 17 56 1 0 17 57 1 0 17 58 1 0 18 59 1 0 18 60 1 0 19 61 1 0 19 62 1 0 20 63 1 1 22 64 1 0 22 65 1 0 22 66 1 0 23 67 1 0 23 68 1 0 23 69 1 0 24 70 1 1 25 71 1 0 25 72 1 0 26 73 1 0 26 74 1 0 28 75 1 0 28 76 1 0 28 77 1 0 29 78 1 0 33 79 1 0 34 80 1 0 34 81 1 0 34 82 1 0 M END

Standard InCHIKey	UVWSKJGMKBMOEV-NYBHINJWSA-N
Standard InCHI	InChI=1S/C30H48O4/c1-18(2)16-19-17-30(33,25(32)34-19)21-10-14-28(6)20(21)8-9-23-27(5)13-12-24(31)26(3,4)22(27)11-15-29(23,28)7/h16,19-24,31,33H,8-15,17H2,1-7H3/t19-,20+,21-,22-,23+,24-,27-,28+,29+,30+/m0/s1
SMILES	CC(=C[C@H]1C[C@@]([C@H]2CC[C@]3(C)[C@@H]2CC[C@@H]2[C@@]4(C)CC[C@@H](C(C)(C)[C@@H]4CC[C@@]32C)O)(C(=O)O1)O)C

Calculated Properties

Physi-Chem Properties

Molecular Weight:	472.36	Volume:	514.542 ? Van der Waals volume.
Dense:	0.918	LogP:	5.206 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	4.326 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-5.405 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	2.0	Rigid Bonds:	27.0
TPSA:	66.76 ? Topological Polar Surface Area.	H-Bond Acceptor:	4.0
H-Bond Donor:	2.0	Rings:	5.0
Heavy Atoms:	4.0

MedChem Properties

QED Drug-Likeness Score:	0.379	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	5.012	Fsp³:	0.9
MCE-18:	102.667 ? MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.	Lipinski Rule-of-5:	Rejected
Pfizer Rule:	Accepted	GSK Rule:	Accepted
Golden Triangle Rule:	Rejected	BMS Rule:	0
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.773	Fluc inhibitor:	0.001 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.002 ? 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:	0.397	Promiscuous compounds:	0.361

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.874	MDCK Permeability:	-4.835
Pgp-inhibitor:	0.604	Pgp-substrate:	0.877
PAMPA:	0.962 ? 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):	0.034
20% Bioavailability (F20%):	0.997	30% Bioavailability (F30%):	0.981
50% Bioavailability (F50%):	1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.153	MRP1:	0.986
Plasma Protein Binding (PPB):	97.721%	Volume Distribution (VD):	0.059
Fu:	3.015% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	1.0
OATP1B3 inhibitor:	0.969	BCRP inhibitor:	0.234
BSEP inhibitor:	0.96

ADMET: Metabolism

CYP1A2-inhibitor:	0.018	CYP1A2-substrate:	0.006
CYP2C19-inhibitor:	0.983	CYP2C19-substrate:	0.005
CYP2C9-inhibitor:	0.008	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.003	CYP2D6-substrate:	0.038
CYP3A4-inhibitor:	0.908	CYP3A4-substrate:	0.996
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.965
HLM stability:	0.858 ? 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):

7.367

Half-life (T1/2):

1.416

ADMET: Toxicity

hERG Blockers:	0.033	hERG Blockers (10um):	0.132
Human Hepatotoxicity (H-HT):	0.678	Drug-induced Liver Injury (DILI):	0.473
AMES Toxicity:	0.618	Rat Oral Acute Toxicity:	0.141
Maximum Recommended Daily Dose:	0.8	Skin Sensitization:	0.999
Carcinogencity:	0.767	Eye Corrosion:	0.028
Eye Irritation:	0.537	Respiratory Toxicity:	0.227
Drug-induced Neurotoxicity:	0.159	Ototoxicity:	0.486
Hematotoxicity:	0.21	Drug-induced Nephrotoxicity:	0.936
Genotoxicity:	0.867	RPMI-8226 Immunitoxicity:	0.11
A549 Cytotoxicity:	0.504	Hek293 Cytotoxicity:	0.232
BCF:	1.886 ? 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:	3.931 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.178 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.72 ? 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
NPO12934	Gynostemma pentaphyllum	Species	Cucurbitaceae	Eukaryota	Stems	n.a.	n.a.	PMID[20104880]
NPO12934	Gynostemma pentaphyllum	Species	Cucurbitaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[22342101]
NPO12934	Gynostemma pentaphyllum	Species	Cucurbitaceae	Eukaryota	aerial parts	n.a.	n.a.	PMID[25895106]
NPO16506	Synotis alata	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO4305	Pertusaria wulfenii	Species	Pertusariaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO12934	Gynostemma pentaphyllum	Species	Cucurbitaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO918	Dahlia pinnata	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO11990	Coleostephus myconis	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO12934	Gynostemma pentaphyllum	Species	Cucurbitaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO11990	Coleostephus myconis	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO918	Dahlia pinnata	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO11990	Coleostephus myconis	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO12934	Gynostemma pentaphyllum	Species	Cucurbitaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO918	Dahlia pinnata	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO11990	Coleostephus myconis	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO12934	Gynostemma pentaphyllum	Species	Cucurbitaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO4305	Pertusaria wulfenii	Species	Pertusariaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO11990	Coleostephus myconis	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO918	Dahlia pinnata	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO16506	Synotis alata	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO12934	Gynostemma pentaphyllum	Species	Cucurbitaceae	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
IC50	1

Activity Type	# Activity
Individual protein	1

Molecular-level activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT178	Individual protein	Protein-tyrosine phosphatase 1B	Homo sapiens	IC50	=	8400.0	nM	PMID[23177789]

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 NPC131665 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	17831
0.1-0.2	24703
0.2-0.3	6633
0.3-0.4	578
0.4-0.5	92
0.5-0.6	18
0.6-0.7	1
0.7-0.8	0
0.8-0.85	0
0.85-0.9	0
0.9-0.95	0
0.95-1	1

Similarity Score	Similarity Level	Natural Product ID
1.0	High Similarity	NPC255387
0.6308	Remote Similarity	NPC112009
0.5968	Remote Similarity	NPC285761
0.5968	Remote Similarity	NPC34930
0.5909	Remote Similarity	NPC201406
0.5781	Remote Similarity	NPC13554
0.5556	Remote Similarity	NPC245869
0.5424	Remote Similarity	NPC232112
0.5323	Remote Similarity	NPC480925
0.5323	Remote Similarity	NPC48079
0.5238	Remote Similarity	NPC606606
0.5231	Remote Similarity	NPC58631
0.5224	Remote Similarity	NPC126993
0.5205	Remote Similarity	NPC607653
0.5152	Remote Similarity	NPC201725
0.5147	Remote Similarity	NPC603388
0.5143	Remote Similarity	NPC483720
0.5075	Remote Similarity	NPC91387
0.5075	Remote Similarity	NPC231680
0.5075	Remote Similarity	NPC270306

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC131665 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	6590
0.1-0.2	2403
0.2-0.3	150
0.3-0.4	6
0.4-0.5	1
0.5-0.6	0
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
		NPD

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