NPASS Compound

Natural Product: NPC154856

Natural Product ID	NPC154856
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Cabenoside D
IUPAC Name	(3S,8S,9R,10R,13R,14S,17R)-17-[(2R,5R)-5,6-dihydroxy-6-methylheptan-2-yl]-4,4,9,13,14-pentamethyl-3-[(2R,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-1,2,3,7,8,10,12,15,16,17-decahydrocyclopenta[a]phenanthren-11-one
Synonyms	cabenoside D
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL510167
PubChem CID	44584114
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0000258] Steroids and steroid derivatives [CHEMONTID:0001013] Steroidal glycosides [CHEMONTID:0002364] Steroidal saponins [CHEMONTID:0001687] Cucurbitacin glycosides

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 105109 0 0 0 0 0 0 0 0999 V2000 5.1701 0.6928 -2.3425 C 0 0 0 0 0 0 0 0 0 0 0 0 4.9112 1.6366 -1.2307 C 0 0 2 0 0 0 0 0 0 0 0 0 6.1072 2.0317 -0.4118 C 0 0 0 0 0 0 0 0 0 0 0 0 6.8566 1.0186 0.3336 C 0 0 0 0 0 0 0 0 0 0 0 0 7.5386 -0.0638 -0.4364 C 0 0 2 0 0 0 0 0 0 0 0 0 8.2721 -1.0242 0.5120 C 0 0 0 0 0 0 0 0 0 0 0 0 8.8161 -2.1472 -0.3224 C 0 0 0 0 0 0 0 0 0 0 0 0 9.3349 -0.3309 1.3013 C 0 0 0 0 0 0 0 0 0 0 0 0 7.3200 -1.5367 1.3771 O 0 0 0 0 0 0 0 0 0 0 0 0 8.5042 0.4598 -1.3248 O 0 0 0 0 0 0 0 0 0 0 0 0 3.8621 1.1632 -0.2571 C 0 0 1 0 0 0 0 0 0 0 0 0 3.7131 2.2655 0.7898 C 0 0 0 0 0 0 0 0 0 0 0 0 2.2316 2.3018 1.1562 C 0 0 0 0 0 0 0 0 0 0 0 0 1.7235 1.0357 0.5706 C 0 0 1 0 0 0 0 0 0 0 0 0 2.2105 -0.1002 1.4132 C 0 0 0 0 0 0 0 0 0 0 0 0 0.2166 1.0160 0.4302 C 0 0 2 0 0 0 0 0 0 0 0 0 -0.3365 1.2548 1.7842 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7146 0.8406 1.9282 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.1828 -0.2534 1.3142 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.2334 -1.0127 0.4824 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.9871 -1.9826 -0.3407 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.3428 -1.3866 -0.7481 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.2649 -1.4509 0.4837 C 0 0 1 0 0 0 0 0 0 0 0 0 -3.6020 -0.6441 1.5552 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.3730 0.6759 1.7552 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.6590 -1.3636 2.9014 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.4407 -0.8577 0.1205 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.5442 -1.6677 0.0692 C 0 0 1 0 0 0 0 0 0 0 0 0 -7.6440 -1.2972 1.0233 C 0 0 1 0 0 0 0 0 0 0 0 0 -8.4158 -0.0824 0.5380 C 0 0 2 0 0 0 0 0 0 0 0 0 -8.0241 0.2694 -0.8847 C 0 0 1 0 0 0 0 0 0 0 0 0 -8.0239 -1.0439 -1.6354 C 0 0 1 0 0 0 0 0 0 0 0 0 -7.8804 -0.7961 -3.1444 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.9356 -0.0793 -3.6603 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.9271 -1.7520 -1.2564 O 0 0 0 0 0 0 0 0 0 0 0 0 -8.9390 1.1615 -1.3911 O 0 0 0 0 0 0 0 0 0 0 0 0 -8.1431 1.0296 1.3295 O 0 0 0 0 0 0 0 0 0 0 0 0 -8.5569 -2.3513 1.0415 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.2805 -0.1539 -0.3161 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.8879 0.2213 -1.6788 C 0 0 0 0 0 0 0 0 0 0 0 0 0.9127 -0.9784 -0.7216 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8731 -2.1820 -0.5548 O 0 0 0 0 0 0 0 0 0 0 0 0 2.1370 -0.3498 -1.3220 C 0 0 0 0 0 0 0 0 0 0 0 0 2.4679 0.9960 -0.7619 C 0 0 2 0 0 0 0 0 0 0 0 0 2.1604 2.1549 -1.6517 C 0 0 0 0 0 0 0 0 0 0 0 0 6.2140 0.7865 -2.7011 H 0 0 0 0 0 0 0 0 0 0 0 0 4.5936 1.0499 -3.2786 H 0 0 0 0 0 0 0 0 0 0 0 0 4.9581 -0.3609 -2.1727 H 0 0 0 0 0 0 0 0 0 0 0 0 4.5982 2.6205 -1.7060 H 0 0 0 0 0 0 0 0 0 0 0 0 5.8147 2.9110 0.2477 H 0 0 0 0 0 0 0 0 0 0 0 0 6.8798 2.5513 -1.0924 H 0 0 0 0 0 0 0 0 0 0 0 0 7.7051 1.5824 0.8577 H 0 0 0 0 0 0 0 0 0 0 0 0 6.2995 0.6044 1.2220 H 0 0 0 0 0 0 0 0 0 0 0 0 6.8867 -0.7151 -1.0270 H 0 0 0 0 0 0 0 0 0 0 0 0 8.0087 -2.8739 -0.5871 H 0 0 0 0 0 0 0 0 0 0 0 0 9.5963 -2.7402 0.2086 H 0 0 0 0 0 0 0 0 0 0 0 0 9.2214 -1.7974 -1.2966 H 0 0 0 0 0 0 0 0 0 0 0 0 10.0127 -1.1253 1.7075 H 0 0 0 0 0 0 0 0 0 0 0 0 9.9748 0.3388 0.7249 H 0 0 0 0 0 0 0 0 0 0 0 0 8.8634 0.1339 2.1926 H 0 0 0 0 0 0 0 0 0 0 0 0 7.8040 -2.1887 1.9739 H 0 0 0 0 0 0 0 0 0 0 0 0 9.0547 1.1422 -0.9086 H 0 0 0 0 0 0 0 0 0 0 0 0 4.3112 0.2489 0.1990 H 0 0 0 0 0 0 0 0 0 0 0 0 3.9043 3.2669 0.3388 H 0 0 0 0 0 0 0 0 0 0 0 0 4.3754 2.1514 1.6435 H 0 0 0 0 0 0 0 0 0 0 0 0 2.1033 2.3233 2.2660 H 0 0 0 0 0 0 0 0 0 0 0 0 1.7316 3.1634 0.6985 H 0 0 0 0 0 0 0 0 0 0 0 0 2.9145 0.2515 2.2266 H 0 0 0 0 0 0 0 0 0 0 0 0 1.4338 -0.6625 1.9573 H 0 0 0 0 0 0 0 0 0 0 0 0 2.7937 -0.8760 0.8751 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.0894 1.9276 -0.1651 H 0 0 0 0 0 0 0 0 0 0 0 0 0.2931 0.8649 2.6154 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.3224 2.3788 1.9830 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.4536 1.3779 2.5363 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.6182 -1.6164 1.2114 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.2762 -2.8533 0.3247 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.4610 -2.4312 -1.1822 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.8125 -1.9510 -1.5537 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.2864 -0.2961 -0.9428 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.3400 -2.5303 0.7034 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.4450 0.5270 1.4838 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.9137 1.4645 1.1361 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.3764 0.8734 2.8402 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.6731 -1.3515 3.3958 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.0140 -2.3932 2.7330 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.3629 -0.8797 3.6044 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.2077 -2.7056 0.3592 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.2528 -1.0336 2.0244 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.5030 -0.2542 0.5513 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.9712 0.6548 -0.9340 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.9530 -1.6367 -1.4506 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.9352 -0.2227 -3.2902 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.7270 -1.7587 -3.6728 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.6789 0.8957 -3.6988 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.8378 0.8745 -1.0882 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.8970 1.2084 1.9408 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.1281 -3.2385 1.0125 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.0460 0.4791 -2.3920 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.5057 1.1230 -1.6322 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.3270 -0.6566 -2.1652 H 0 0 0 0 0 0 0 0 0 0 0 0 2.9684 -1.0804 -1.1481 H 0 0 0 0 0 0 0 0 0 0 0 0 1.9215 -0.2678 -2.4191 H 0 0 0 0 0 0 0 0 0 0 0 0 2.4165 1.8447 -2.6973 H 0 0 0 0 0 0 0 0 0 0 0 0 2.6695 3.0918 -1.3517 H 0 0 0 0 0 0 0 0 0 0 0 0 1.0926 2.4481 -1.7114 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 6 9 1 0 5 10 1 0 2 11 1 0 11 12 1 0 12 13 1 0 13 14 1 0 14 15 1 1 14 16 1 0 16 17 1 0 17 18 1 0 18 19 2 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 24 26 1 0 23 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 33 34 1 0 32 35 1 0 31 36 1 0 30 37 1 0 29 38 1 0 20 39 1 0 39 40 1 6 39 41 1 0 41 42 2 0 41 43 1 0 43 44 1 0 44 45 1 6 44 11 1 0 44 14 1 0 39 16 1 0 24 19 1 0 35 28 1 0 1 46 1 0 1 47 1 0 1 48 1 0 2 49 1 6 3 50 1 0 3 51 1 0 4 52 1 0 4 53 1 0 5 54 1 6 7 55 1 0 7 56 1 0 7 57 1 0 8 58 1 0 8 59 1 0 8 60 1 0 9 61 1 0 10 62 1 0 11 63 1 1 12 64 1 0 12 65 1 0 13 66 1 0 13 67 1 0 15 68 1 0 15 69 1 0 15 70 1 0 16 71 1 6 17 72 1 0 17 73 1 0 18 74 1 0 20 75 1 1 21 76 1 0 21 77 1 0 22 78 1 0 22 79 1 0 23 80 1 1 25 81 1 0 25 82 1 0 25 83 1 0 26 84 1 0 26 85 1 0 26 86 1 0 28 87 1 1 29 88 1 1 30 89 1 6 31 90 1 1 32 91 1 6 33 92 1 0 33 93 1 0 34 94 1 0 36 95 1 0 37 96 1 0 38 97 1 0 40 98 1 0 40 99 1 0 40100 1 0 43101 1 0 43102 1 0 45103 1 0 45104 1 0 45105 1 0 M END

Standard InCHIKey	XMWIWVZEGGOMAU-CDPRDXQRSA-N
Standard InCHI	InChI=1S/C36H60O9/c1-19(9-13-25(38)33(4,5)43)20-15-16-34(6)24-12-10-21-22(36(24,8)26(39)17-35(20,34)7)11-14-27(32(21,2)3)45-31-30(42)29(41)28(40)23(18-37)44-31/h10,19-20,22-25,27-31,37-38,40-43H,9,11-18H2,1-8H3/t19-,20-,22-,23-,24+,25-,27+,28-,29+,30-,31+,34+,35-,36+/m1/s1
SMILES	C[C@H](CC[C@H](C(C)(C)O)O)[C@H]1CC[C@@]2(C)[C@@H]3CC=C4[C@@H](CC[C@@H](C4(C)C)O[C@H]4[C@@H]([C@H]([C@@H]([C@@H](CO)O4)O)O)O)[C@]3(C)C(=O)C[C@]12C

Calculated Properties

Physi-Chem Properties

Molecular Weight:	636.42	Volume:	662.269 ? Van der Waals volume.
Dense:	0.961	LogP:	3.362 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.678 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.764 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	8.0	Rigid Bonds:	27.0
TPSA:	156.91 ? Topological Polar Surface Area.	H-Bond Acceptor:	9.0
H-Bond Donor:	6.0	Rings:	5.0
Heavy Atoms:	9.0

MedChem Properties

QED Drug-Likeness Score:	0.22	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	5.465	Fsp³:	0.917
MCE-18:	109.681 ? 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:	0
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.915	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:	0.22	Promiscuous compounds:	0.297

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.581	MDCK Permeability:	-5.141
Pgp-inhibitor:	0.02	Pgp-substrate:	0.106
PAMPA:	0.968 ? 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%):	0.008	30% Bioavailability (F30%):	0.221
50% Bioavailability (F50%):	0.991

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.112	MRP1:	0.158
Plasma Protein Binding (PPB):	80.739%	Volume Distribution (VD):	-0.307
Fu:	14.95% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	1.0
OATP1B3 inhibitor:	1.0	BCRP inhibitor:	0.609
BSEP inhibitor:	0.168

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.002	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.0	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.02
CYP3A4-inhibitor:	1.0	CYP3A4-substrate:	0.995
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	1.0
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):

2.411

Half-life (T1/2):

1.794

ADMET: Toxicity

hERG Blockers:	0.025	hERG Blockers (10um):	0.043
Human Hepatotoxicity (H-HT):	0.701	Drug-induced Liver Injury (DILI):	0.644
AMES Toxicity:	0.731	Rat Oral Acute Toxicity:	0.032
Maximum Recommended Daily Dose:	0.083	Skin Sensitization:	0.998
Carcinogencity:	0.443	Eye Corrosion:	0.0
Eye Irritation:	0.006	Respiratory Toxicity:	0.041
Drug-induced Neurotoxicity:	0.015	Ototoxicity:	0.98
Hematotoxicity:	0.578	Drug-induced Nephrotoxicity:	0.908
Genotoxicity:	0.72	RPMI-8226 Immunitoxicity:	0.103
A549 Cytotoxicity:	0.391	Hek293 Cytotoxicity:	0.458
BCF:	1.293 ? 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:	3.556 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.119 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.381 ? 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
NPO33132	bryonia dioica	Species	Cucurbitaceae	Eukaryota	Roots	n.a.	n.a.	PMID[11858752]
NPO33132	bryonia dioica	Species	Cucurbitaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[17503850]

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
Inhibition	4
Activity	2
ID50	1

Activity Type	# Activity
Cell line	1
Organism	2
Others	4

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
NPT80	Cell line	Raji	Homo sapiens	Activity	=	60.0	%	PMID[23398362]
NPT2	Others	Unspecified	n.a.	Inhibition	=	0.0	%	PMID[15808482]
NPT2	Others	Unspecified	n.a.	Inhibition	=	26.1	%	PMID[23252603]
NPT2	Others	Unspecified	n.a.	Inhibition	=	69.3	%	PMID[17603540]
NPT2	Others	Unspecified	n.a.	Inhibition	=	94.1	%	DrugMatrix in vivo data: Pathology

In vivo activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT32	Organism	Mus musculus	Mus musculus	ID50	=	0.6	mg	PMID[18183025]
NPT32	Organism	Mus musculus	Mus musculus	Activity	=	66.0	%	PMID[23117171]

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 NPC154856 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	18549
0.1-0.2	24799
0.2-0.3	5442
0.3-0.4	1000
0.4-0.5	43
0.5-0.6	8
0.6-0.7	8
0.7-0.8	0
0.8-0.85	2
0.85-0.9	1
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.8553	High Similarity	NPC130427
0.8312	Intermediate Similarity	NPC74727
0.8193	Intermediate Similarity	NPC474265
0.7831	Intermediate Similarity	NPC485578
0.7647	Intermediate Similarity	NPC279638
0.7303	Intermediate Similarity	NPC473882
0.7143	Intermediate Similarity	NPC485579
0.7079	Intermediate Similarity	NPC474557
0.6633	Remote Similarity	NPC485580
0.6548	Remote Similarity	NPC34562
0.6548	Remote Similarity	NPC52241
0.6429	Remote Similarity	NPC221562
0.6353	Remote Similarity	NPC187400
0.631	Remote Similarity	NPC75608
0.6196	Remote Similarity	NPC210420
0.6044	Remote Similarity	NPC309448
0.5974	Remote Similarity	NPC32830
0.5914	Remote Similarity	NPC190395
0.5909	Remote Similarity	NPC475317
0.5699	Remote Similarity	NPC606839
0.5556	Remote Similarity	NPC302057
0.53	Remote Similarity	NPC168899
0.53	Remote Similarity	NPC69273
0.5055	Remote Similarity	NPC93352

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC154856 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	6871
0.1-0.2	2187
0.2-0.3	88
0.3-0.4	4
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