NPASS Compound

Natural Product: NPC475633

Natural Product ID	NPC475633
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	2-Beta, 27-Dihydroxy-23-Carboxyoleanolic Acid-3-O-Beta-D-Glucopyranoside
IUPAC Name	(4aS,6aR,6aR,6bR,8aR,9R,10R,11S,12aR,14bS)-9-(carboxymethyl)-11-hydroxy-6a-(hydroxymethyl)-2,2,6b,9,12a-pentamethyl-10-[(2R,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-1,3,4,5,6,6a,7,8,8a,10,11,12,13,14b-tetradecahydropicene-4a-carboxylic acid
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL509835
PubChem CID	44575292
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0000259] Prenol lipids [CHEMONTID:0002049] Terpene glycosides [CHEMONTID:0001580] Triterpene glycosides [CHEMONTID:0002358] Triterpene saponins

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 107112 0 0 0 0 0 0 0 0999 V2000 -7.2781 -2.9251 -1.4742 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.6063 -1.5661 -1.4783 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.5582 -0.5750 -0.9143 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.9325 0.7613 -0.5883 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.7668 0.5384 0.4204 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.1902 1.8625 0.7557 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.7271 2.0543 0.4424 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.8769 0.8758 0.8544 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.4865 -0.3623 0.2871 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.6992 -1.4415 0.3350 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.3189 -1.4429 0.8947 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.5861 -0.1768 0.5452 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.5136 0.9450 0.2629 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8783 2.2909 0.4905 C 0 0 0 0 0 0 0 0 0 0 0 0 0.5881 2.2508 0.0054 C 0 0 0 0 0 0 0 0 0 0 0 0 1.3758 1.3172 0.9424 C 0 0 0 0 0 0 0 0 0 0 0 0 0.6406 0.1113 1.3642 C 0 0 0 0 0 0 0 0 0 0 0 0 1.4814 -1.1809 1.2950 C 0 0 0 0 0 0 0 0 0 0 0 0 2.8872 -0.9372 1.7502 C 0 0 0 0 0 0 0 0 0 0 0 0 3.4934 -0.0793 0.6885 C 0 0 0 0 0 0 0 0 0 0 0 0 2.8055 1.2551 0.5828 C 0 0 0 0 0 0 0 0 0 0 0 0 3.5787 2.2907 1.4553 C 0 0 0 0 0 0 0 0 0 0 0 0 3.1652 1.7629 -0.7941 C 0 0 0 0 0 0 0 0 0 0 0 0 2.6475 1.1259 -1.9640 C 0 0 0 0 0 0 0 0 0 0 0 0 2.7842 1.7361 -3.0669 O 0 0 0 0 0 0 0 0 0 0 0 0 2.0052 -0.0857 -2.0869 O 0 0 0 0 0 0 0 0 0 0 0 0 4.8626 0.0145 0.7575 O 0 0 0 0 0 0 0 0 0 0 0 0 5.6014 -0.5458 -0.2328 C 0 0 0 0 0 0 0 0 0 0 0 0 6.3972 -1.7036 0.3804 C 0 0 0 0 0 0 0 0 0 0 0 0 7.7842 -1.8222 -0.1629 C 0 0 0 0 0 0 0 0 0 0 0 0 7.8433 -1.4567 -1.6334 C 0 0 0 0 0 0 0 0 0 0 0 0 7.1501 -0.1353 -1.8890 C 0 0 0 0 0 0 0 0 0 0 0 0 6.5580 0.3464 -0.7161 O 0 0 0 0 0 0 0 0 0 0 0 0 8.1685 0.8875 -2.3276 C 0 0 0 0 0 0 0 0 0 0 0 0 7.4818 2.0800 -2.5520 O 0 0 0 0 0 0 0 0 0 0 0 0 7.3656 -2.4789 -2.4344 O 0 0 0 0 0 0 0 0 0 0 0 0 8.2409 -3.1507 -0.0627 O 0 0 0 0 0 0 0 0 0 0 0 0 6.5096 -1.4329 1.7421 O 0 0 0 0 0 0 0 0 0 0 0 0 3.5108 -2.2091 1.6972 O 0 0 0 0 0 0 0 0 0 0 0 0 0.3627 0.1800 2.8556 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7591 0.8966 -1.2463 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.8204 -0.3546 -0.3335 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.3508 -1.7023 -0.6363 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.9762 0.8271 2.3280 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.5156 1.9620 2.9960 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.4370 -0.1577 1.5510 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.1428 -1.2692 2.0107 O 0 0 0 0 0 0 0 0 0 0 0 0 -7.5115 0.5368 2.1422 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.2183 -1.2688 -2.9146 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.6324 -3.6002 -2.0845 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.2197 -3.3031 -0.4335 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.3133 -2.8657 -1.8385 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.9764 -0.9858 0.0252 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.3796 -0.4029 -1.6099 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.6097 1.3431 -1.4507 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.6807 1.3504 -0.0260 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.4671 2.1256 1.8015 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.7217 2.6704 0.1634 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.6366 2.3508 -0.5917 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.3882 2.9139 1.0700 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.0941 -2.3650 -0.0515 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.8210 -2.3391 0.3896 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.2847 -1.7386 1.9524 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.1080 -0.4243 -0.4507 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.3408 3.1032 -0.1091 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.8903 2.6363 1.5343 H 0 0 0 0 0 0 0 0 0 0 0 0 0.6362 1.9783 -1.0388 H 0 0 0 0 0 0 0 0 0 0 0 0 0.9537 3.2769 0.2219 H 0 0 0 0 0 0 0 0 0 0 0 0 1.3570 1.9761 1.9014 H 0 0 0 0 0 0 0 0 0 0 0 0 1.0081 -1.9377 1.9265 H 0 0 0 0 0 0 0 0 0 0 0 0 1.5241 -1.5580 0.2588 H 0 0 0 0 0 0 0 0 0 0 0 0 3.0302 -0.5932 2.7631 H 0 0 0 0 0 0 0 0 0 0 0 0 3.2773 -0.6233 -0.2601 H 0 0 0 0 0 0 0 0 0 0 0 0 3.6412 1.9594 2.4873 H 0 0 0 0 0 0 0 0 0 0 0 0 3.0347 3.2397 1.3574 H 0 0 0 0 0 0 0 0 0 0 0 0 4.5949 2.4380 1.0578 H 0 0 0 0 0 0 0 0 0 0 0 0 4.2808 1.7663 -0.8447 H 0 0 0 0 0 0 0 0 0 0 0 0 2.9122 2.8563 -0.7794 H 0 0 0 0 0 0 0 0 0 0 0 0 2.2637 -0.7399 -2.8344 H 0 0 0 0 0 0 0 0 0 0 0 0 5.0049 -1.0262 -1.0382 H 0 0 0 0 0 0 0 0 0 0 0 0 5.8220 -2.6525 0.3024 H 0 0 0 0 0 0 0 0 0 0 0 0 8.5147 -1.1653 0.3589 H 0 0 0 0 0 0 0 0 0 0 0 0 8.9148 -1.3259 -1.8768 H 0 0 0 0 0 0 0 0 0 0 0 0 6.4200 -0.3102 -2.6966 H 0 0 0 0 0 0 0 0 0 0 0 0 8.7384 0.5576 -3.2188 H 0 0 0 0 0 0 0 0 0 0 0 0 8.8847 1.0261 -1.4934 H 0 0 0 0 0 0 0 0 0 0 0 0 6.9304 2.0648 -3.3491 H 0 0 0 0 0 0 0 0 0 0 0 0 7.5437 -3.3391 -1.9392 H 0 0 0 0 0 0 0 0 0 0 0 0 8.7932 -3.2067 0.7631 H 0 0 0 0 0 0 0 0 0 0 0 0 6.7216 -0.4757 1.9196 H 0 0 0 0 0 0 0 0 0 0 0 0 3.3401 -2.5499 0.7931 H 0 0 0 0 0 0 0 0 0 0 0 0 1.2518 -0.0746 3.4711 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.4242 -0.4776 3.2153 H 0 0 0 0 0 0 0 0 0 0 0 0 0.1042 1.2162 3.1581 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.7447 0.6489 -1.6896 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.9897 1.8766 -1.6738 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.3948 0.0772 -1.5638 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.7672 0.1646 -1.3640 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.6014 -2.1728 -1.3598 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.4233 -2.4185 0.1758 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.7177 -0.1281 2.8170 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.0894 0.8812 2.5687 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.4523 1.7356 3.9428 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.1175 0.0355 2.7841 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.1667 -1.5313 -3.1189 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.8430 -1.8788 -3.6123 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.3413 -0.1839 -3.1069 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 2 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 19 20 1 0 20 21 1 0 21 22 1 0 21 23 1 0 23 24 1 0 24 25 2 0 24 26 1 0 20 27 1 0 27 28 1 0 28 29 1 0 29 30 1 0 30 31 1 0 31 32 1 0 32 33 1 0 32 34 1 0 34 35 1 0 31 36 1 0 30 37 1 0 29 38 1 0 19 39 1 0 17 40 1 0 13 41 1 0 9 42 1 0 42 43 1 0 8 44 1 0 44 45 1 0 5 46 1 0 46 47 2 0 46 48 1 0 2 49 1 0 43 2 1 0 42 5 1 0 13 8 1 0 17 12 1 0 21 16 1 0 33 28 1 0 1 50 1 0 1 51 1 0 1 52 1 0 3 53 1 0 3 54 1 0 4 55 1 0 4 56 1 0 6 57 1 0 6 58 1 0 7 59 1 0 7 60 1 0 10 61 1 0 11 62 1 0 11 63 1 0 12 64 1 0 14 65 1 0 14 66 1 0 15 67 1 0 15 68 1 0 16 69 1 0 18 70 1 0 18 71 1 0 19 72 1 0 20 73 1 0 22 74 1 0 22 75 1 0 22 76 1 0 23 77 1 0 23 78 1 0 26 79 1 0 28 80 1 0 29 81 1 0 30 82 1 0 31 83 1 0 32 84 1 0 34 85 1 0 34 86 1 0 35 87 1 0 36 88 1 0 37 89 1 0 38 90 1 0 39 91 1 0 40 92 1 0 40 93 1 0 40 94 1 0 41 95 1 0 41 96 1 0 41 97 1 0 42 98 1 0 43 99 1 0 43100 1 0 44101 1 0 44102 1 0 45103 1 0 48104 1 0 49105 1 0 49106 1 0 49107 1 0 M END

Standard InCHIKey	BNZZGNKTVHWPDP-SAVRTDBWSA-N
Standard InCHI	InChI=1S/C37H58O12/c1-32(2)10-11-36(31(46)47)12-13-37(18-39)19(20(36)14-32)6-7-24-33(3)15-21(40)29(49-30-28(45)27(44)26(43)22(17-38)48-30)34(4,16-25(41)42)23(33)8-9-35(24,37)5/h6,20-24,26-30,38-40,43-45H,7-18H2,1-5H3,(H,41,42)(H,46,47)/t20-,21-,22+,23+,24+,26+,27-,28+,29-,30-,33-,34+,35+,36-,37-/m0/s1
SMILES	CC1(CCC2(CCC3(C(=CCC4C3(CCC5C4(CC(C(C5(C)CC(=O)O)OC6C(C(C(C(O6)CO)O)O)O)O)C)C)C2C1)CO)C(=O)O)C

Calculated Properties

Physi-Chem Properties

Molecular Weight:	694.39	Volume:	694.743 ? Van der Waals volume.
Dense:	0.999	LogP:	1.712 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.186 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.684 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	7.0	Rigid Bonds:	34.0
TPSA:	214.44 ? Topological Polar Surface Area.	H-Bond Acceptor:	12.0
H-Bond Donor:	8.0	Rings:	6.0
Heavy Atoms:	12.0

MedChem Properties

QED Drug-Likeness Score:	0.143	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	5.642	Fsp³:	0.892
MCE-18:	133.0 ? 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:	0.065	Fluc inhibitor:	0.0 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.006 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.378 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.101	Promiscuous compounds:	0.002

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-6.5	MDCK Permeability:	-5.186
Pgp-inhibitor:	0.0	Pgp-substrate:	0.028
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):	0.487
20% Bioavailability (F20%):	0.008	30% Bioavailability (F30%):	0.041
50% Bioavailability (F50%):	0.905

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.032	MRP1:	1.0
Plasma Protein Binding (PPB):	66.434%	Volume Distribution (VD):	-0.515
Fu:	24.845% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.0
OATP1B3 inhibitor:	0.19	BCRP inhibitor:	0.0
BSEP inhibitor:	0.0

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.001	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	1.0	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.0
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	0.0
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.0
HLM stability:	0.0 ? 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):

0.644

Half-life (T1/2):

3.168

ADMET: Toxicity

hERG Blockers:	0.005	hERG Blockers (10um):	0.007
Human Hepatotoxicity (H-HT):	0.542	Drug-induced Liver Injury (DILI):	0.409
AMES Toxicity:	0.05	Rat Oral Acute Toxicity:	0.181
Maximum Recommended Daily Dose:	0.167	Skin Sensitization:	0.057
Carcinogencity:	0.025	Eye Corrosion:	0.0
Eye Irritation:	0.001	Respiratory Toxicity:	0.022
Drug-induced Neurotoxicity:	0.032	Ototoxicity:	0.999
Hematotoxicity:	0.088	Drug-induced Nephrotoxicity:	0.416
Genotoxicity:	0.117	RPMI-8226 Immunitoxicity:	0.021
A549 Cytotoxicity:	0.001	Hek293 Cytotoxicity:	0.04
BCF:	0.24 ? 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:	3.678 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.762 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	3.907 ? 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
NPO11905	Polygala japonica	Species	Polygalaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[16643032]
NPO11905	Polygala japonica	Species	Polygalaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO11905	Polygala japonica	Species	Polygalaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO11905	Polygala japonica	Species	Polygalaceae	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
Activity	2

Activity Type	# Activity
Organism	2

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
NPT32	Organism	Mus musculus	Mus musculus	Activity	=	36.2	%	PMID[15387639]
NPT32	Organism	Mus musculus	Mus musculus	Activity	=	17.8	%	PMID[25981689]

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 NPC475633 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	21931
0.1-0.2	22987
0.2-0.3	3797
0.3-0.4	905
0.4-0.5	180
0.5-0.6	46
0.6-0.7	4
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
0.6591	Remote Similarity	NPC204407
0.6517	Remote Similarity	NPC606107
0.6196	Remote Similarity	NPC31839
0.6146	Remote Similarity	NPC164194
0.5979	Remote Similarity	NPC270667
0.596	Remote Similarity	NPC59804
0.59	Remote Similarity	NPC127056
0.5859	Remote Similarity	NPC136877
0.5859	Remote Similarity	NPC12288
0.5842	Remote Similarity	NPC472949
0.58	Remote Similarity	NPC25605
0.5783	Remote Similarity	NPC198664
0.5769	Remote Similarity	NPC473383
0.5743	Remote Similarity	NPC109079
0.5673	Remote Similarity	NPC114304
0.5631	Remote Similarity	NPC80843
0.5631	Remote Similarity	NPC22956
0.5588	Remote Similarity	NPC480424
0.5566	Remote Similarity	NPC139044
0.5514	Remote Similarity	NPC257468
0.5474	Remote Similarity	NPC57362
0.5472	Remote Similarity	NPC180550
0.5472	Remote Similarity	NPC35405
0.5455	Remote Similarity	NPC488209
0.5413	Remote Similarity	NPC276093
0.5385	Remote Similarity	NPC488561
0.5364	Remote Similarity	NPC323359
0.5364	Remote Similarity	NPC324875
0.5364	Remote Similarity	NPC292677
0.534	Remote Similarity	NPC174679
0.534	Remote Similarity	NPC279554
0.5321	Remote Similarity	NPC79718
0.5321	Remote Similarity	NPC119794
0.5315	Remote Similarity	NPC488564
0.5312	Remote Similarity	NPC28198
0.5312	Remote Similarity	NPC476123
0.5287	Remote Similarity	NPC271614
0.5221	Remote Similarity	NPC62725
0.5196	Remote Similarity	NPC127853
0.5192	Remote Similarity	NPC56713
0.5175	Remote Similarity	NPC288205
0.5175	Remote Similarity	NPC51465
0.5155	Remote Similarity	NPC283849
0.5133	Remote Similarity	NPC475486
0.5098	Remote Similarity	NPC473481
0.5094	Remote Similarity	NPC488516
0.5051	Remote Similarity	NPC286347
0.5043	Remote Similarity	NPC323341
0.5043	Remote Similarity	NPC133818
0.5043	Remote Similarity	NPC476992

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC475633 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	6704
0.1-0.2	2362
0.2-0.3	79
0.3-0.4	5
0.4-0.5	0
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