NPASS Compound

Natural Product: NPC476221

Natural Product ID	NPC476221
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	QHTLPWXBPOENQB-KTGBMRPESA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL555674
PubChem CID	45269892
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 99106 0 0 0 0 0 0 0 0999 V2000 -5.4789 -1.4880 -3.7828 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.0257 -1.4946 -3.3416 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.7246 -0.2398 -2.5947 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.0431 -0.4655 -1.1524 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.1073 -1.5384 -0.6453 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.7973 -2.5725 -1.6950 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.7881 -2.6654 -2.6651 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.5823 -2.4105 -2.3064 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.4879 -2.2913 -1.4877 C 0 0 0 0 0 0 0 0 0 0 0 0 0.5258 -1.4025 -2.1636 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8405 -0.1666 -1.3979 C 0 0 0 0 0 0 0 0 0 0 0 0 1.8888 0.6253 -2.0915 C 0 0 0 0 0 0 0 0 0 0 0 0 3.2003 -0.0529 -2.0498 C 0 0 0 0 0 0 0 0 0 0 0 0 3.5111 -0.8735 -0.8405 C 0 0 0 0 0 0 0 0 0 0 0 0 2.6160 -0.7152 0.3272 C 0 0 0 0 0 0 0 0 0 0 0 0 1.1919 -0.3593 0.0449 C 0 0 0 0 0 0 0 0 0 0 0 0 0.2244 -1.3088 0.7276 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8762 -1.8029 -0.1277 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.9220 -0.8966 -0.2874 O 0 0 0 0 0 0 0 0 0 0 0 0 0.9241 0.9917 0.6793 C 0 0 0 0 0 0 0 0 0 0 0 0 0.1218 1.1512 1.5829 O 0 0 0 0 0 0 0 0 0 0 0 0 3.2164 0.1884 1.4151 C 0 0 0 0 0 0 0 0 0 0 0 0 4.1993 1.1657 0.8750 C 0 0 0 0 0 0 0 0 0 0 0 0 5.3839 0.4096 0.3206 C 0 0 0 0 0 0 0 0 0 0 0 0 4.9661 -0.7394 -0.5422 C 0 0 0 0 0 0 0 0 0 0 0 0 5.4836 -2.0149 0.0609 C 0 0 0 0 0 0 0 0 0 0 0 0 6.7701 -1.5221 0.7426 C 0 0 0 0 0 0 0 0 0 0 0 0 6.2416 -0.2327 1.3539 C 0 0 0 0 0 0 0 0 0 0 0 0 7.4010 0.5686 1.8103 C 0 0 0 0 0 0 0 0 0 0 0 0 8.6800 0.2462 1.7080 C 0 0 0 0 0 0 0 0 0 0 0 0 9.5235 1.2901 2.2704 C 0 0 0 0 0 0 0 0 0 0 0 0 10.7834 1.3121 2.3401 O 0 0 0 0 0 0 0 0 0 0 0 0 8.6723 2.2826 2.7280 O 0 0 0 0 0 0 0 0 0 0 0 0 7.3597 1.8842 2.4955 C 0 0 0 0 0 0 0 0 0 0 0 0 5.6114 -0.5609 -1.7905 O 0 0 0 0 0 0 0 0 0 0 0 0 6.2187 1.4245 -0.4395 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.6047 -2.1403 0.5095 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.9828 0.7125 -0.4526 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.1872 1.0838 0.1195 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.7265 2.3966 -0.4062 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.2045 2.4301 0.0058 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.2676 2.3190 1.5082 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.3864 1.2317 2.0528 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.1438 1.1631 1.4880 O 0 0 0 0 0 0 0 0 0 0 0 0 -7.1508 -0.0753 2.0250 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.4792 -1.0768 2.7088 O 0 0 0 0 0 0 0 0 0 0 0 0 -8.5769 2.0149 1.8845 O 0 0 0 0 0 0 0 0 0 0 0 0 -7.8000 3.6231 -0.3912 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.1347 3.4710 0.2988 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.1561 -1.8994 -3.0063 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.7922 -0.5097 -4.1793 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.5496 -2.2099 -4.6465 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.4397 -1.4329 -4.3038 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.6789 0.0831 -2.7714 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.4119 0.5518 -2.9914 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.0818 -0.8749 -1.1031 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.7997 -3.5625 -1.1945 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.0689 -3.3153 -1.3541 H 0 0 0 0 0 0 0 0 0 0 0 0 1.3978 -2.0250 -2.4404 H 0 0 0 0 0 0 0 0 0 0 0 0 0.1171 -1.0540 -3.1580 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.0946 0.4742 -1.4160 H 0 0 0 0 0 0 0 0 0 0 0 0 1.5548 0.7542 -3.1620 H 0 0 0 0 0 0 0 0 0 0 0 0 1.9988 1.6630 -1.7068 H 0 0 0 0 0 0 0 0 0 0 0 0 3.2959 -0.6581 -3.0027 H 0 0 0 0 0 0 0 0 0 0 0 0 3.9895 0.7424 -2.1993 H 0 0 0 0 0 0 0 0 0 0 0 0 3.4193 -1.9546 -1.1882 H 0 0 0 0 0 0 0 0 0 0 0 0 2.5765 -1.7279 0.8454 H 0 0 0 0 0 0 0 0 0 0 0 0 0.8444 -2.1620 1.1094 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.2365 -0.8703 1.6461 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.3291 -2.6883 0.4102 H 0 0 0 0 0 0 0 0 0 0 0 0 1.4385 1.8857 0.3557 H 0 0 0 0 0 0 0 0 0 0 0 0 3.7214 -0.4009 2.2133 H 0 0 0 0 0 0 0 0 0 0 0 0 2.4164 0.7343 1.9822 H 0 0 0 0 0 0 0 0 0 0 0 0 4.5427 1.7975 1.6904 H 0 0 0 0 0 0 0 0 0 0 0 0 3.8114 1.7804 0.0379 H 0 0 0 0 0 0 0 0 0 0 0 0 4.8291 -2.4373 0.8315 H 0 0 0 0 0 0 0 0 0 0 0 0 5.7619 -2.7132 -0.7443 H 0 0 0 0 0 0 0 0 0 0 0 0 7.1117 -2.2143 1.5117 H 0 0 0 0 0 0 0 0 0 0 0 0 7.4843 -1.3161 -0.0535 H 0 0 0 0 0 0 0 0 0 0 0 0 5.7222 -0.5520 2.2801 H 0 0 0 0 0 0 0 0 0 0 0 0 9.0992 -0.6667 1.2691 H 0 0 0 0 0 0 0 0 0 0 0 0 6.8841 1.6779 3.4935 H 0 0 0 0 0 0 0 0 0 0 0 0 6.7700 2.6493 1.9409 H 0 0 0 0 0 0 0 0 0 0 0 0 5.3095 -1.2951 -2.3619 H 0 0 0 0 0 0 0 0 0 0 0 0 5.8669 2.4835 -0.2599 H 0 0 0 0 0 0 0 0 0 0 0 0 7.2436 1.3932 -0.0245 H 0 0 0 0 0 0 0 0 0 0 0 0 6.2198 1.2400 -1.5367 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.3808 -1.5293 1.2717 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.9311 0.2983 -0.1467 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.6089 2.5338 -1.4781 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.6929 1.5991 -0.5181 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.0415 3.3109 1.9267 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.2422 1.4731 3.1476 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.0944 0.1272 2.6136 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.4665 -0.3723 1.0143 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.1330 -1.7486 3.0113 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.2447 2.5448 1.3668 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.4643 4.3550 0.1841 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.5646 3.1583 1.0251 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 1 0 15 16 1 0 16 17 1 0 17 18 1 0 18 19 1 0 16 20 1 0 20 21 2 0 15 22 1 0 22 23 1 0 23 24 1 0 24 25 1 0 25 26 1 0 26 27 1 0 27 28 1 0 28 29 1 0 29 30 2 0 30 31 1 0 31 32 2 0 31 33 1 0 33 34 1 0 25 35 1 0 24 36 1 0 5 37 1 0 4 38 1 0 38 39 1 0 39 40 1 0 40 41 1 0 41 42 1 0 42 43 1 0 43 44 1 0 43 45 1 0 45 46 1 0 42 47 1 0 41 48 1 0 40 49 1 0 7 2 1 0 19 5 1 0 18 9 1 0 16 11 1 0 25 14 1 0 28 24 1 0 34 29 1 0 44 39 1 0 1 50 1 0 1 51 1 0 1 52 1 0 2 53 1 0 3 54 1 0 3 55 1 0 4 56 1 0 6 57 1 0 9 58 1 0 10 59 1 0 10 60 1 0 11 61 1 0 12 62 1 0 12 63 1 0 13 64 1 0 13 65 1 0 14 66 1 0 15 67 1 0 17 68 1 0 17 69 1 0 18 70 1 0 20 71 1 0 22 72 1 0 22 73 1 0 23 74 1 0 23 75 1 0 26 76 1 0 26 77 1 0 27 78 1 0 27 79 1 0 28 80 1 0 30 81 1 0 34 82 1 0 34 83 1 0 35 84 1 0 36 85 1 0 36 86 1 0 36 87 1 0 37 88 1 0 39 89 1 0 40 90 1 0 41 91 1 0 42 92 1 0 43 93 1 0 45 94 1 0 45 95 1 0 46 96 1 0 47 97 1 0 48 98 1 0 49 99 1 0 M END

Standard InCHIKey	QHTLPWXBPOENQB-KTGBMRPESA-N
Standard InCHI	InChI=1S/C35H50O14/c1-16-9-25(48-30-29(41)28(40)27(39)24(13-36)46-30)35(43)31(45-16)47-22-11-18-3-4-21-20(33(18,15-37)12-23(22)49-35)5-7-32(2)19(6-8-34(21,32)42)17-10-26(38)44-14-17/h10,15-16,18-25,27-31,36,39-43H,3-9,11-14H2,1-2H3/t16-,18+,19-,20+,21-,22-,23-,24-,25-,27-,28+,29-,30-,31+,32-,33-,34+,35+/m1/s1
SMILES	CC1CC(C2(C(O1)OC3CC4CCC5C(C4(CC3O2)C=O)CCC6(C5(CCC6C7=CC(=O)OC7)O)C)O)OC8C(C(C(C(O8)CO)O)O)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	694.32	Volume:	660.618 ? Van der Waals volume.
Dense:	1.051	LogP:	0.156 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	0.856 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-2.543 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	5.0	Rigid Bonds:	43.0
TPSA:	210.9 ? Topological Polar Surface Area.	H-Bond Acceptor:	14.0
H-Bond Donor:	6.0	Rings:	8.0
Heavy Atoms:	14.0

MedChem Properties

QED Drug-Likeness Score:	0.125	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	5.988	Fsp³:	0.886
MCE-18:	148.121 ? MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.	Lipinski Rule-of-5:	Accepted
Pfizer Rule:	Rejected	GSK Rule:	Accepted
Golden Triangle Rule:	Accepted	BMS Rule:	1
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.013	Fluc inhibitor:	0.0 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.013 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.22 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.289	Promiscuous compounds:	0.003

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-6.485	MDCK Permeability:	-5.092
Pgp-inhibitor:	0.0	Pgp-substrate:	0.908
PAMPA:	1.0 ? 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):	1.0
20% Bioavailability (F20%):	0.79	30% Bioavailability (F30%):	0.998
50% Bioavailability (F50%):	0.999

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.001	MRP1:	0.997
Plasma Protein Binding (PPB):	57.029%	Volume Distribution (VD):	-0.447
Fu:	38.76% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.0
OATP1B3 inhibitor:	0.122	BCRP inhibitor:	0.0
BSEP inhibitor:	0.224

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.881	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.997	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.0
CYP3A4-inhibitor:	0.196	CYP3A4-substrate:	0.0
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.0
HLM stability:	0.001 ? 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):

0.937

Half-life (T1/2):

3.585

ADMET: Toxicity

hERG Blockers:	0.079	hERG Blockers (10um):	0.206
Human Hepatotoxicity (H-HT):	0.83	Drug-induced Liver Injury (DILI):	0.41
AMES Toxicity:	0.982	Rat Oral Acute Toxicity:	0.929
Maximum Recommended Daily Dose:	0.964	Skin Sensitization:	0.967
Carcinogencity:	0.276	Eye Corrosion:	0.0
Eye Irritation:	0.0	Respiratory Toxicity:	0.086
Drug-induced Neurotoxicity:	0.793	Ototoxicity:	0.999
Hematotoxicity:	0.122	Drug-induced Nephrotoxicity:	0.261
Genotoxicity:	1.0	RPMI-8226 Immunitoxicity:	0.779
A549 Cytotoxicity:	0.099	Hek293 Cytotoxicity:	0.96
BCF:	0.452 ? 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:	3.669 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.619 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.212 ? 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
NPO33139	Pergularia tomentosa	Species	Apocynaceae	Eukaryota	roots	Wadi Um Hebal, Egypt	2001-JAN	PMID[16989527]
NPO33139	Pergularia tomentosa	Species	Apocynaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[19555122]
NPO33139	Pergularia tomentosa	Species	Apocynaceae	Eukaryota	Aerial Parts	n.a.	n.a.	PMID[30629433]
NPO33139	Pergularia tomentosa	Species	Apocynaceae	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

Activity Type	# Activity
IC50	7

Activity Type	# Activity
Cell line	5
Non-molecular	1
Others	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
NPT306	Cell line	PC-3	Homo sapiens	IC50	=	200.0	nM	Open TG-GATES in vivo data: Organ Weight
NPT1081	Cell line	BXPC-3	Homo sapiens	IC50	=	500.0	nM	Open TG-GATES in vivo data: Organ Weight
NPT114	Cell line	LoVo	Homo sapiens	IC50	=	400.0	nM	Open TG-GATES in vivo data: Organ Weight
NPT81	Cell line	A549	Homo sapiens	IC50	=	200.0	nM	PMID[22260257]
NPT83	Cell line	MCF7	Homo sapiens	IC50	=	300.0	nM	Open TG-GATES in vivo data: Organ Weight
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	IC50	=	400.0	nM	PMID[19555122]
NPT2	Others	Unspecified	n.a.	IC50	=	500.0	nM	Open TG-GATES in vivo data: Organ Weight

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 NPC476221 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	16943
0.1-0.2	28240
0.2-0.3	4245
0.3-0.4	225
0.4-0.5	107
0.5-0.6	61
0.6-0.7	25
0.7-0.8	0
0.8-0.85	1
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	NPC477709
0.8161	Intermediate Similarity	NPC91
0.6989	Remote Similarity	NPC298783
0.6848	Remote Similarity	NPC253456
0.6848	Remote Similarity	NPC159338
0.6739	Remote Similarity	NPC480914
0.6667	Remote Similarity	NPC171619
0.6632	Remote Similarity	NPC488161
0.6632	Remote Similarity	NPC16569
0.6598	Remote Similarity	NPC142756
0.6596	Remote Similarity	NPC277374
0.6495	Remote Similarity	NPC163365
0.6364	Remote Similarity	NPC188234
0.6238	Remote Similarity	NPC85369
0.6117	Remote Similarity	NPC329986
0.6117	Remote Similarity	NPC140092
0.6105	Remote Similarity	NPC5311
0.6105	Remote Similarity	NPC77299
0.6105	Remote Similarity	NPC480906
0.6078	Remote Similarity	NPC125077
0.6078	Remote Similarity	NPC480905
0.6078	Remote Similarity	NPC470094
0.6058	Remote Similarity	NPC486138
0.6058	Remote Similarity	NPC276838
0.6019	Remote Similarity	NPC473040
0.6019	Remote Similarity	NPC232785
0.6019	Remote Similarity	NPC486139
0.596	Remote Similarity	NPC480907
0.5941	Remote Similarity	NPC292467
0.5938	Remote Similarity	NPC469750
0.5938	Remote Similarity	NPC480915
0.58	Remote Similarity	NPC329905
0.5784	Remote Similarity	NPC236973
0.5784	Remote Similarity	NPC32177
0.5784	Remote Similarity	NPC469756
0.5784	Remote Similarity	NPC275901
0.5728	Remote Similarity	NPC480910
0.5728	Remote Similarity	NPC240070
0.5728	Remote Similarity	NPC480909
0.5714	Remote Similarity	NPC104585
0.5686	Remote Similarity	NPC30483
0.5686	Remote Similarity	NPC470897
0.5676	Remote Similarity	NPC486150
0.566	Remote Similarity	NPC247190
0.5644	Remote Similarity	NPC488162
0.5644	Remote Similarity	NPC93416
0.5588	Remote Similarity	NPC157817
0.5556	Remote Similarity	NPC76572
0.5556	Remote Similarity	NPC193382
0.5545	Remote Similarity	NPC42670
0.5545	Remote Similarity	NPC19124
0.5534	Remote Similarity	NPC33934
0.5514	Remote Similarity	NPC486146
0.551	Remote Similarity	NPC84987
0.5495	Remote Similarity	NPC74259
0.5472	Remote Similarity	NPC486143
0.5472	Remote Similarity	NPC486135
0.5472	Remote Similarity	NPC486142
0.5472	Remote Similarity	NPC486137
0.5472	Remote Similarity	NPC486149
0.5446	Remote Similarity	NPC474908
0.5429	Remote Similarity	NPC225385
0.5429	Remote Similarity	NPC32793
0.5429	Remote Similarity	NPC116075
0.5408	Remote Similarity	NPC99620
0.54	Remote Similarity	NPC243196
0.5385	Remote Similarity	NPC488158
0.5385	Remote Similarity	NPC488159
0.5354	Remote Similarity	NPC196429
0.5347	Remote Similarity	NPC146456
0.5288	Remote Similarity	NPC474466
0.5278	Remote Similarity	NPC469749
0.5234	Remote Similarity	NPC610296
0.5229	Remote Similarity	NPC146857
0.5221	Remote Similarity	NPC475419
0.5179	Remote Similarity	NPC486144
0.5179	Remote Similarity	NPC486145
0.5179	Remote Similarity	NPC486147
0.5179	Remote Similarity	NPC475590
0.5179	Remote Similarity	NPC486136
0.5179	Remote Similarity	NPC486148
0.5175	Remote Similarity	NPC486134
0.5175	Remote Similarity	NPC486141
0.5088	Remote Similarity	NPC120390
0.5049	Remote Similarity	NPC88668
0.5049	Remote Similarity	NPC250556
0.5048	Remote Similarity	NPC609258
0.5043	Remote Similarity	NPC474423

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC476221 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	6672
0.1-0.2	2396
0.2-0.3	66
0.3-0.4	8
0.4-0.5	5
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
0.5566	Remote Similarity	NPD7625	Phase 1
0.5049	Remote Similarity	NPD7507	Pre-clinical

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