NPASS Compound

Natural Product: NPC1980

Natural Product ID	NPC1980
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Cucurbitacin J 2-O-Beta-D-Glucopyranoside
IUPAC Name	(8S,9R,10R,13R,14S,16R,17R)-16-hydroxy-4,4,9,13,14-pentamethyl-2-[(2S,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-17-[(2R,5R)-2,5,6-trihydroxy-6-methyl-3-oxoheptan-2-yl]-8,10,12,15,16,17-hexahydro-7H-cyclopenta[a]phenanthrene-3,11-dione
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL1923786
PubChem CID	6324996
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 103107 0 0 0 0 0 0 0 0999 V2000 -3.7698 -3.5166 1.7642 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.5733 -3.4253 0.2572 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.8110 -4.8112 -0.3114 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.2334 -2.9144 -0.0402 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.2286 -3.7964 -0.2034 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0997 -3.1871 -0.5036 C 0 0 0 0 0 0 0 0 0 0 0 0 0.3355 -2.1863 0.6400 C 0 0 1 0 0 0 0 0 0 0 0 0 1.6682 -1.5462 0.3464 C 0 0 2 0 0 0 0 0 0 0 0 0 1.6982 -1.2007 -1.0901 C 0 0 0 0 0 0 0 0 0 0 0 0 2.8371 -2.4987 0.5744 C 0 0 0 0 0 0 0 0 0 0 0 0 3.9986 -1.5315 0.6552 C 0 0 2 0 0 0 0 0 0 0 0 0 3.4397 -0.1492 0.9110 C 0 0 1 0 0 0 0 0 0 0 0 0 2.0398 -0.4622 1.3190 C 0 0 2 0 0 0 0 0 0 0 0 0 2.0918 -1.0178 2.7191 C 0 0 0 0 0 0 0 0 0 0 0 0 1.0529 0.6415 1.1889 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.2256 0.2216 0.4998 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.7625 1.0246 -0.2107 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.7470 -1.1689 0.7437 C 0 0 2 0 0 0 0 0 0 0 0 0 -1.3693 -1.1182 2.1401 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.8890 -1.4845 -0.1861 C 0 0 2 0 0 0 0 0 0 0 0 0 -3.0472 -0.5894 0.0238 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.2850 -1.0391 -0.0254 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.5470 -2.4444 -0.2886 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.5683 -2.8209 -0.9588 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.3969 -0.2194 0.1651 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.0792 0.4105 -0.8979 C 0 0 1 0 0 0 0 0 0 0 0 0 -7.3767 1.0054 -0.5004 C 0 0 1 0 0 0 0 0 0 0 0 0 -7.4231 2.4804 -0.3323 C 0 0 2 0 0 0 0 0 0 0 0 0 -6.3476 3.2373 -1.0257 C 0 0 1 0 0 0 0 0 0 0 0 0 -5.8267 2.3306 -2.1499 C 0 0 1 0 0 0 0 0 0 0 0 0 -4.8852 3.0577 -3.0492 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.8583 3.5912 -2.2861 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.1739 1.2963 -1.4802 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.8554 4.3964 -1.5635 O 0 0 0 0 0 0 0 0 0 0 0 0 -7.4377 2.7419 1.0587 O 0 0 0 0 0 0 0 0 0 0 0 0 -8.3475 0.6698 -1.4751 O 0 0 0 0 0 0 0 0 0 0 0 0 4.2806 0.6470 1.8520 C 0 0 2 0 0 0 0 0 0 0 0 0 3.7078 2.0394 2.1049 C 0 0 0 0 0 0 0 0 0 0 0 0 5.5790 0.9131 1.1494 C 0 0 0 0 0 0 0 0 0 0 0 0 6.6112 0.6036 1.7043 O 0 0 0 0 0 0 0 0 0 0 0 0 5.6458 1.5379 -0.1902 C 0 0 0 0 0 0 0 0 0 0 0 0 7.0702 1.6933 -0.6631 C 0 0 2 0 0 0 0 0 0 0 0 0 7.0965 2.3385 -2.0378 C 0 0 0 0 0 0 0 0 0 0 0 0 6.4623 3.7031 -2.0253 C 0 0 0 0 0 0 0 0 0 0 0 0 6.3735 1.4740 -3.0524 C 0 0 0 0 0 0 0 0 0 0 0 0 8.4164 2.4520 -2.4669 O 0 0 0 0 0 0 0 0 0 0 0 0 7.6535 0.4412 -0.7905 O 0 0 0 0 0 0 0 0 0 0 0 0 4.4816 0.1061 3.1015 O 0 0 0 0 0 0 0 0 0 0 0 0 4.7255 -1.6435 -0.5032 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.6801 -4.1570 1.8983 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.0597 -2.5235 2.1515 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.8960 -3.9272 2.2816 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.9220 -4.9578 -0.3188 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.4279 -5.5579 0.4371 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.4016 -4.9583 -1.3089 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.4208 -4.8379 -0.1146 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.0124 -2.6973 -1.4834 H 0 0 0 0 0 0 0 0 0 0 0 0 0.9249 -3.9115 -0.4524 H 0 0 0 0 0 0 0 0 0 0 0 0 0.3286 -2.8187 1.5390 H 0 0 0 0 0 0 0 0 0 0 0 0 2.4589 -0.5178 -1.4551 H 0 0 0 0 0 0 0 0 0 0 0 0 0.7379 -0.8186 -1.5168 H 0 0 0 0 0 0 0 0 0 0 0 0 1.9357 -2.1702 -1.6366 H 0 0 0 0 0 0 0 0 0 0 0 0 2.9524 -3.1866 -0.2981 H 0 0 0 0 0 0 0 0 0 0 0 0 2.7334 -3.0479 1.5155 H 0 0 0 0 0 0 0 0 0 0 0 0 4.6487 -1.8762 1.4871 H 0 0 0 0 0 0 0 0 0 0 0 0 3.3888 0.4833 -0.0095 H 0 0 0 0 0 0 0 0 0 0 0 0 3.0222 -1.6304 2.9005 H 0 0 0 0 0 0 0 0 0 0 0 0 1.9972 -0.2182 3.4948 H 0 0 0 0 0 0 0 0 0 0 0 0 1.2876 -1.7404 2.9610 H 0 0 0 0 0 0 0 0 0 0 0 0 0.7007 0.8994 2.2327 H 0 0 0 0 0 0 0 0 0 0 0 0 1.4343 1.5604 0.7400 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.4246 -0.7867 2.0819 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.8575 -0.3625 2.7714 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.3589 -2.1243 2.5913 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.5783 -1.3682 -1.2584 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.9456 0.4717 0.2295 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.2556 -0.3878 -1.6532 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.7228 0.4688 0.4152 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.4163 2.8844 -0.6888 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.5148 3.4106 -0.3132 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.6849 1.8680 -2.6884 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.4795 3.8703 -3.5551 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.5366 2.3707 -3.8287 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.1500 4.4391 -1.8572 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.8150 4.5389 -1.3714 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.6404 2.3653 1.4848 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.2404 0.5601 -1.0799 H 0 0 0 0 0 0 0 0 0 0 0 0 3.5384 2.6057 1.1790 H 0 0 0 0 0 0 0 0 0 0 0 0 2.7647 2.0081 2.6837 H 0 0 0 0 0 0 0 0 0 0 0 0 4.4404 2.5525 2.7825 H 0 0 0 0 0 0 0 0 0 0 0 0 5.0920 1.0319 -0.9768 H 0 0 0 0 0 0 0 0 0 0 0 0 5.2268 2.5884 -0.1567 H 0 0 0 0 0 0 0 0 0 0 0 0 7.5926 2.3468 0.0462 H 0 0 0 0 0 0 0 0 0 0 0 0 5.4451 3.7122 -2.4797 H 0 0 0 0 0 0 0 0 0 0 0 0 7.0928 4.4158 -2.6278 H 0 0 0 0 0 0 0 0 0 0 0 0 6.4256 4.1193 -0.9930 H 0 0 0 0 0 0 0 0 0 0 0 0 6.9149 1.5052 -4.0339 H 0 0 0 0 0 0 0 0 0 0 0 0 5.3219 1.7571 -3.1814 H 0 0 0 0 0 0 0 0 0 0 0 0 6.4047 0.3950 -2.7390 H 0 0 0 0 0 0 0 0 0 0 0 0 8.4676 2.4287 -3.4657 H 0 0 0 0 0 0 0 0 0 0 0 0 8.2309 0.2862 0.0204 H 0 0 0 0 0 0 0 0 0 0 0 0 5.3357 0.4970 3.4624 H 0 0 0 0 0 0 0 0 0 0 0 0 4.2963 -2.1406 -1.2282 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 1 0 2 4 1 0 4 5 2 0 5 6 1 0 6 7 1 0 7 8 1 0 8 9 1 6 8 10 1 0 10 11 1 0 11 12 1 0 12 13 1 0 13 14 1 1 13 15 1 0 15 16 1 0 16 17 2 0 16 18 1 0 18 19 1 1 18 20 1 0 20 21 1 0 21 22 2 0 22 23 1 0 23 24 2 0 22 25 1 0 25 26 1 0 26 27 1 0 27 28 1 0 28 29 1 0 29 30 1 0 30 31 1 0 31 32 1 0 30 33 1 0 29 34 1 0 28 35 1 0 27 36 1 0 12 37 1 0 37 38 1 0 37 39 1 0 39 40 2 0 39 41 1 0 41 42 1 0 42 43 1 0 43 44 1 0 43 45 1 0 43 46 1 0 42 47 1 0 37 48 1 1 11 49 1 0 23 2 1 0 33 26 1 0 20 4 1 0 18 7 1 0 13 8 1 0 1 50 1 0 1 51 1 0 1 52 1 0 3 53 1 0 3 54 1 0 3 55 1 0 5 56 1 0 6 57 1 0 6 58 1 0 7 59 1 1 9 60 1 0 9 61 1 0 9 62 1 0 10 63 1 0 10 64 1 0 11 65 1 1 12 66 1 6 14 67 1 0 14 68 1 0 14 69 1 0 15 70 1 0 15 71 1 0 19 72 1 0 19 73 1 0 19 74 1 0 20 75 1 6 21 76 1 0 26 77 1 6 27 78 1 1 28 79 1 6 29 80 1 1 30 81 1 6 31 82 1 0 31 83 1 0 32 84 1 0 34 85 1 0 35 86 1 0 36 87 1 0 38 88 1 0 38 89 1 0 38 90 1 0 41 91 1 0 41 92 1 0 42 93 1 1 44 94 1 0 44 95 1 0 44 96 1 0 45 97 1 0 45 98 1 0 45 99 1 0 46100 1 0 47101 1 0 48102 1 0 49103 1 0 M END

Standard InCHIKey	XPEAYHKXEWXAKV-WOVCZDRSSA-N
Standard InCHI	InChI=1S/C36H54O13/c1-31(2)16-9-10-21-33(5)13-18(38)28(36(8,47)23(40)12-22(39)32(3,4)46)34(33,6)14-24(41)35(21,7)17(16)11-19(29(31)45)48-30-27(44)26(43)25(42)20(15-37)49-30/h9,11,17-18,20-22,25-28,30,37-39,42-44,46-47H,10,12-15H2,1-8H3/t17-,18-,20-,21+,22-,25-,26+,27-,28+,30-,33+,34-,35+,36+/m1/s1
SMILES	CC1(C)C2=CC[C@H]3[C@]4(C)C[C@H]([C@@H]([C@@]4(C)CC(=O)[C@@]3(C)[C@@H]2C=C(C1=O)O[C@H]1[C@@H]([C@H]([C@@H]([C@@H](CO)O1)O)O)O)[C@](C)(C(=O)C[C@H](C(C)(C)O)O)O)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	694.36	Volume:	689.52 ? Van der Waals volume.
Dense:	1.007	LogP:	0.166 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	1.207 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-2.439 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	8.0	Rigid Bonds:	29.0
TPSA:	231.51 ? Topological Polar Surface Area.	H-Bond Acceptor:	13.0
H-Bond Donor:	8.0	Rings:	5.0
Heavy Atoms:	13.0

MedChem Properties

QED Drug-Likeness Score:	0.158	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	5.855	Fsp³:	0.806
MCE-18:	119.631 ? 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:	0.673	Fluc inhibitor:	0.01 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.116 ? 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:	0.199	Promiscuous compounds:	0.444

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.822	MDCK Permeability:	-5.093
Pgp-inhibitor:	0.0	Pgp-substrate:	0.022
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):	0.054
20% Bioavailability (F20%):	0.004	30% Bioavailability (F30%):	0.443
50% Bioavailability (F50%):	0.994

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.0	MRP1:	0.655
Plasma Protein Binding (PPB):	81.588%	Volume Distribution (VD):	-0.111
Fu:	14.671% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	1.0
OATP1B3 inhibitor:	1.0	BCRP inhibitor:	0.004
BSEP inhibitor:	0.363

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.0	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.0
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	0.448
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.982
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):

1.845

Half-life (T1/2):

3.244

ADMET: Toxicity

hERG Blockers:	0.001	hERG Blockers (10um):	0.005
Human Hepatotoxicity (H-HT):	0.649	Drug-induced Liver Injury (DILI):	0.693
AMES Toxicity:	0.776	Rat Oral Acute Toxicity:	0.017
Maximum Recommended Daily Dose:	0.194	Skin Sensitization:	0.999
Carcinogencity:	0.558	Eye Corrosion:	0.0
Eye Irritation:	0.0	Respiratory Toxicity:	0.027
Drug-induced Neurotoxicity:	0.003	Ototoxicity:	0.987
Hematotoxicity:	0.697	Drug-induced Nephrotoxicity:	0.994
Genotoxicity:	0.994	RPMI-8226 Immunitoxicity:	0.284
A549 Cytotoxicity:	0.1	Hek293 Cytotoxicity:	0.205
BCF:	0.436 ? 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:	3.098 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.647 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	3.82 ? 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
NPO30742	Machilus yaoshansis	Species	Lauraceae	Eukaryota	root	Dayao Mountain, Guangxi, China	2007-DEC	PMID[22044245]
NPO30742	Machilus yaoshansis	Species	Lauraceae	Eukaryota	n.a.	root	n.a.	PMID[22044245]
NPO30742	Machilus yaoshansis	Species	Lauraceae	Eukaryota	Roots	n.a.	n.a.	PMID[22779787]
NPO30742	Machilus yaoshansis	Species	Lauraceae	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	5

Activity Type	# Activity
Cell line	4
Non-molecular	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
NPT179	Cell line	A2780	Homo sapiens	IC50	>	10000.0	nM	PMID[22044245]
NPT180	Cell line	HCT-8	Homo sapiens	IC50	>	10000.0	nM	PMID[22044245]
NPT181	Cell line	Bel-7402	Homo sapiens	IC50	>	10000.0	nM	PMID[22044245]
NPT81	Cell line	A549	Homo sapiens	IC50	>	10000.0	nM	PMID[22044245]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	IC50	>	10000.0	nM	PMID[22044245]

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 NPC1980 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	19829
0.1-0.2	26174
0.2-0.3	3585
0.3-0.4	227
0.4-0.5	28
0.5-0.6	4
0.6-0.7	3
0.7-0.8	0
0.8-0.85	2
0.85-0.9	1
0.9-0.95	0
0.95-1	1

Similarity Score	Similarity Level	Natural Product ID
1.0	High Similarity	NPC141196
0.859	High Similarity	NPC42675
0.8481	Intermediate Similarity	NPC238005
0.8125	Intermediate Similarity	NPC152091
0.7701	Intermediate Similarity	NPC803
0.7662	Intermediate Similarity	NPC216866
0.7558	Intermediate Similarity	NPC213634
0.7051	Intermediate Similarity	NPC31797
0.6941	Remote Similarity	NPC93368
0.6782	Remote Similarity	NPC198714
0.6	Remote Similarity	NPC190846
0.5833	Remote Similarity	NPC277191
0.5679	Remote Similarity	NPC58370
0.5679	Remote Similarity	NPC43285
0.5301	Remote Similarity	NPC117185

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC1980 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	7031
0.1-0.2	2077
0.2-0.3	42
0.3-0.4	0
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