NPASS Compound

Natural Product: NPC470826

Natural Product ID	NPC470826
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	5''-Methoxyhedyotisol A
IUPAC Name	(1S,2R)-2-[4-[(3R,3aS,6R,6aS)-6-[4-[(1S,2R)-1,3-dihydroxy-1-(4-hydroxy-3,5-dimethoxyphenyl)propan-2-yl]oxy-3,5-dimethoxyphenyl]-1,3,3a,4,6,6a-hexahydrofuro[3,4-c]furan-3-yl]-2,6-dimethoxyphenoxy]-1-(4-hydroxy-3-methoxyphenyl)propane-1,3-diol
Synonyms	5'-Methoxyhedyotisol A
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL225480
PubChem CID	44421289
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0001392] Lignans, neolignans and related compounds [CHEMONTID:0003686] Furanoid lignans

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 112117 0 0 0 0 0 0 0 0999 V2000 8.7223 -1.6384 -2.3559 O 0 0 0 0 0 0 0 0 0 0 0 0 8.4093 -0.2380 -2.4674 C 0 0 0 0 0 0 0 0 0 0 0 0 7.5533 0.0767 -1.2580 C 0 0 2 0 0 0 0 0 0 0 0 0 8.5148 0.0587 -0.0689 C 0 0 2 0 0 0 0 0 0 0 0 0 9.5542 1.1175 -0.2257 C 0 0 0 0 0 0 0 0 0 0 0 0 9.3703 2.2440 -1.0972 C 0 0 0 0 0 0 0 0 0 0 0 0 10.3463 3.1584 -1.1555 C 0 0 0 0 0 0 0 0 0 0 0 0 11.5308 3.1595 -0.4720 C 0 0 0 0 0 0 0 0 0 0 0 0 11.7480 2.0932 0.3745 C 0 0 0 0 0 0 0 0 0 0 0 0 10.7379 1.0941 0.4728 C 0 0 0 0 0 0 0 0 0 0 0 0 12.8682 1.9545 1.1462 O 0 0 0 0 0 0 0 0 0 0 0 0 13.2174 1.0039 2.0760 C 0 0 0 0 0 0 0 0 0 0 0 0 12.4865 4.1620 -0.5666 O 0 0 0 0 0 0 0 0 0 0 0 0 9.1336 -1.1860 -0.0152 O 0 0 0 0 0 0 0 0 0 0 0 0 6.4914 -0.6786 -1.2205 O 0 0 0 0 0 0 0 0 0 0 0 0 5.3790 -1.1605 -0.7062 C 0 0 0 0 0 0 0 0 0 0 0 0 5.1781 -2.5013 -0.3919 C 0 0 0 0 0 0 0 0 0 0 0 0 6.2278 -3.2823 -0.6228 O 0 0 0 0 0 0 0 0 0 0 0 0 7.1491 -4.1527 -0.7804 C 0 0 0 0 0 0 0 0 0 0 0 0 3.9868 -2.9424 0.1337 C 0 0 0 0 0 0 0 0 0 0 0 0 2.9356 -2.0221 0.3566 C 0 0 0 0 0 0 0 0 0 0 0 0 3.1447 -0.7221 0.0593 C 0 0 0 0 0 0 0 0 0 0 0 0 4.3000 -0.2430 -0.4489 C 0 0 0 0 0 0 0 0 0 0 0 0 4.6827 1.0469 -0.7551 O 0 0 0 0 0 0 0 0 0 0 0 0 3.9664 2.2061 -0.2831 C 0 0 0 0 0 0 0 0 0 0 0 0 1.6166 -2.6569 0.5273 C 0 0 2 0 0 0 0 0 0 0 0 0 1.2706 -3.0536 -0.8849 O 0 0 0 0 0 0 0 0 0 0 0 0 0.7919 -1.8840 -1.4082 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.1333 -1.2726 -0.3274 C 0 0 2 0 0 0 0 0 0 0 0 0 0.3565 -2.0112 0.8854 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.7010 -3.0975 1.0268 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.6545 -2.9529 0.0694 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.5379 -1.7052 -0.5403 C 0 0 1 0 0 0 0 0 0 0 0 0 -2.6019 -0.7942 -0.0493 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.0280 -0.8966 1.2548 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.0373 -0.1194 1.7428 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.4915 -0.2429 3.0569 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.9191 -1.3750 3.7391 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.6901 0.8184 0.9761 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.2979 0.9531 -0.3434 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.2479 0.1323 -0.8282 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.9095 1.8258 -1.2026 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.5534 1.7998 -2.6043 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.6753 1.5926 1.4742 O 0 0 0 0 0 0 0 0 0 0 0 0 -7.0213 1.6586 1.1360 C 0 0 1 0 0 0 0 0 0 0 0 0 -7.5824 0.1962 1.0674 C 0 0 2 0 0 0 0 0 0 0 0 0 -8.8106 0.3371 0.2879 C 0 0 0 0 0 0 0 0 0 0 0 0 -10.1090 0.3974 0.6934 C 0 0 0 0 0 0 0 0 0 0 0 0 -11.2967 0.5786 0.2215 C 0 0 0 0 0 0 0 0 0 0 0 0 -12.4820 0.6836 0.2823 O 0 0 0 0 0 0 0 0 0 0 0 0 -13.8905 0.8059 0.3698 C 0 0 0 0 0 0 0 0 0 0 0 0 -11.0371 0.7852 -1.4008 C 0 0 0 0 0 0 0 0 0 0 0 0 -9.8230 0.7326 -1.8266 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.6831 0.5190 -1.1472 C 0 0 0 0 0 0 0 0 0 0 0 0 -9.6736 0.9863 -3.2910 O 0 0 0 0 0 0 0 0 0 0 0 0 -8.2787 1.1468 -3.5792 C 0 0 0 0 0 0 0 0 0 0 0 0 -12.2228 1.0067 -2.0055 O 0 0 0 0 0 0 0 0 0 0 0 0 -7.7054 -0.4157 2.2549 O 0 0 0 0 0 0 0 0 0 0 0 0 -7.8399 2.4090 2.1707 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.8986 1.6747 3.3768 O 0 0 0 0 0 0 0 0 0 0 0 0 8.0309 -2.0875 -2.8779 H 0 0 0 0 0 0 0 0 0 0 0 0 7.9432 -0.1188 -3.4201 H 0 0 0 0 0 0 0 0 0 0 0 0 9.4499 0.2248 -2.3736 H 0 0 0 0 0 0 0 0 0 0 0 0 7.2112 1.1624 -1.3474 H 0 0 0 0 0 0 0 0 0 0 0 0 7.8919 0.2398 0.8242 H 0 0 0 0 0 0 0 0 0 0 0 0 8.4617 2.2883 -1.6577 H 0 0 0 0 0 0 0 0 0 0 0 0 10.2259 4.0403 -1.8415 H 0 0 0 0 0 0 0 0 0 0 0 0 10.9208 0.2686 1.1125 H 0 0 0 0 0 0 0 0 0 0 0 0 12.2843 0.5409 2.5289 H 0 0 0 0 0 0 0 0 0 0 0 0 13.9021 0.2396 1.7254 H 0 0 0 0 0 0 0 0 0 0 0 0 13.7313 1.5390 2.9587 H 0 0 0 0 0 0 0 0 0 0 0 0 12.6478 4.5959 0.3873 H 0 0 0 0 0 0 0 0 0 0 0 0 9.1153 -1.5221 0.9165 H 0 0 0 0 0 0 0 0 0 0 0 0 7.2277 -4.4686 -1.9071 H 0 0 0 0 0 0 0 0 0 0 0 0 7.1402 -5.1096 -0.1930 H 0 0 0 0 0 0 0 0 0 0 0 0 8.1803 -3.6491 -0.6088 H 0 0 0 0 0 0 0 0 0 0 0 0 3.8104 -3.9764 0.3735 H 0 0 0 0 0 0 0 0 0 0 0 0 2.2930 -0.0231 0.2631 H 0 0 0 0 0 0 0 0 0 0 0 0 4.8252 2.7808 0.2783 H 0 0 0 0 0 0 0 0 0 0 0 0 3.7168 2.7450 -1.2057 H 0 0 0 0 0 0 0 0 0 0 0 0 3.2022 1.9523 0.4221 H 0 0 0 0 0 0 0 0 0 0 0 0 1.7559 -3.6703 1.0100 H 0 0 0 0 0 0 0 0 0 0 0 0 0.2564 -2.1281 -2.3405 H 0 0 0 0 0 0 0 0 0 0 0 0 1.6251 -1.1886 -1.7073 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.0041 -0.1756 -0.2969 H 0 0 0 0 0 0 0 0 0 0 0 0 0.4507 -1.3741 1.7437 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.1575 -4.0841 0.7945 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.0279 -3.1970 2.0514 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.7124 -1.8778 -1.6274 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.5294 -1.5775 1.9009 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.2162 -2.2776 3.0137 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.8962 -1.4123 3.8098 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.4931 -1.6359 4.6442 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.9397 0.2341 -1.8804 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.2238 2.4202 -3.1938 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.4953 1.9066 -2.8252 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.7781 0.7008 -2.9365 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.1747 2.0781 0.1354 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.8216 -0.2918 0.3948 H 0 0 0 0 0 0 0 0 0 0 0 0 -10.1388 0.1394 1.8554 H 0 0 0 0 0 0 0 0 0 0 0 0 -14.2512 -0.0673 0.8980 H 0 0 0 0 0 0 0 0 0 0 0 0 -14.2725 1.0734 -0.6010 H 0 0 0 0 0 0 0 0 0 0 0 0 -14.0673 1.6687 1.1613 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.6940 0.4364 -1.5122 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.6452 0.3135 -3.5314 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.1099 1.7706 -4.5056 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.9435 1.8482 -2.6750 H 0 0 0 0 0 0 0 0 0 0 0 0 -12.3959 1.3294 -2.9364 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.9292 -1.0536 2.3223 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.8854 2.6507 1.8536 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.3419 3.4071 2.3704 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.9921 1.2018 3.4210 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 2 0 6 7 1 0 7 8 2 0 8 9 1 0 9 10 2 0 9 11 1 0 11 12 1 0 8 13 1 0 4 14 1 0 3 15 1 0 15 16 1 0 16 17 2 0 17 18 1 0 18 19 1 0 17 20 1 0 20 21 2 0 21 22 1 0 22 23 2 0 23 24 1 0 24 25 1 0 21 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 32 33 1 0 33 34 1 0 34 35 2 0 35 36 1 0 36 37 1 0 37 38 1 0 36 39 2 0 39 40 1 0 40 41 2 0 40 42 1 0 42 43 1 0 39 44 1 0 44 45 1 0 45 46 1 0 46 47 1 0 47 48 2 0 48 49 1 0 49 50 1 0 50 51 1 0 49 52 2 0 52 53 1 0 53 54 2 0 53 55 1 0 55 56 1 0 52 57 1 0 46 58 1 0 45 59 1 0 59 60 1 0 10 5 1 0 23 16 1 0 30 26 1 0 41 34 1 0 54 47 1 0 33 29 1 0 1 61 1 0 2 62 1 0 2 63 1 0 3 64 1 6 4 65 1 1 6 66 1 0 7 67 1 0 10 68 1 0 12 69 1 0 12 70 1 0 12 71 1 0 13 72 1 0 14 73 1 0 19 74 1 0 19 75 1 0 19 76 1 0 20 77 1 0 22 78 1 0 25 79 1 0 25 80 1 0 25 81 1 0 26 82 1 1 28 83 1 0 28 84 1 0 29 85 1 1 30 86 1 1 31 87 1 0 31 88 1 0 33 89 1 6 35 90 1 0 38 91 1 0 38 92 1 0 38 93 1 0 41 94 1 0 43 95 1 0 43 96 1 0 43 97 1 0 45 98 1 6 46 99 1 6 48100 1 0 51101 1 0 51102 1 0 51103 1 0 54104 1 0 56105 1 0 56106 1 0 56107 1 0 57108 1 0 58109 1 0 59110 1 0 59111 1 0 60112 1 0 M END

Standard InCHIKey	PNQYLBUPZLUYBF-APUQJHFSSA-N
Standard InCHI	InChI=1S/C43H52O17/c1-50-28-10-21(8-9-27(28)46)37(47)35(17-44)59-42-31(53-4)13-23(14-32(42)54-5)40-25-19-58-41(26(25)20-57-40)24-15-33(55-6)43(34(16-24)56-7)60-36(18-45)38(48)22-11-29(51-2)39(49)30(12-22)52-3/h8-16,25-26,35-38,40-41,44-49H,17-20H2,1-7H3/t25-,26-,35-,36-,37+,38+,40+,41+/m1/s1
SMILES	OC[C@H]([C@H](c1ccc(c(c1)OC)O)O)Oc1c(OC)cc(cc1OC)[C@@H]1OC[C@@H]2[C@H]1CO[C@H]2c1cc(OC)c(c(c1)OC)O[C@@H]([C@H](c1cc(OC)c(c(c1)OC)O)O)CO

Calculated Properties

Physi-Chem Properties

Molecular Weight:	840.32	Volume:	818.741 ? Van der Waals volume.
Dense:	1.026	LogP:	0.533 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	0.967 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-2.84 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	19.0	Rigid Bonds:	33.0
TPSA:	222.91 ? Topological Polar Surface Area.	H-Bond Acceptor:	17.0
H-Bond Donor:	6.0	Rings:	6.0
Heavy Atoms:	17.0

MedChem Properties

QED Drug-Likeness Score:	0.078	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	5.086	Fsp³:	0.442
MCE-18:	130.935 ? 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:	1	PAINS Alert:	0
Colloidal aggregators:	0.631	Fluc inhibitor:	0.328 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.012 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.289 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.092	Promiscuous compounds:	0.601

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.46	MDCK Permeability:	-5.12
Pgp-inhibitor:	0.196	Pgp-substrate:	0.07
PAMPA:	0.009 ? 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%):	0.002	30% Bioavailability (F30%):	0.003
50% Bioavailability (F50%):	0.964

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.002	MRP1:	0.98
Plasma Protein Binding (PPB):	83.408%	Volume Distribution (VD):	-0.032
Fu:	18.841% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	1.0
OATP1B3 inhibitor:	1.0	BCRP inhibitor:	0.814
BSEP inhibitor:	0.804

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	1.0	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.0	CYP2C9-substrate:	0.315
CYP2D6-inhibitor:	0.15	CYP2D6-substrate:	0.001
CYP3A4-inhibitor:	1.0	CYP3A4-substrate:	0.001
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	1.0
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):

5.299

Half-life (T1/2):

3.769

ADMET: Toxicity

hERG Blockers:	0.056	hERG Blockers (10um):	0.12
Human Hepatotoxicity (H-HT):	0.985	Drug-induced Liver Injury (DILI):	0.969
AMES Toxicity:	0.658	Rat Oral Acute Toxicity:	0.073
Maximum Recommended Daily Dose:	0.315	Skin Sensitization:	0.997
Carcinogencity:	0.178	Eye Corrosion:	0.0
Eye Irritation:	0.001	Respiratory Toxicity:	0.013
Drug-induced Neurotoxicity:	0.87	Ototoxicity:	0.981
Hematotoxicity:	0.444	Drug-induced Nephrotoxicity:	0.953
Genotoxicity:	0.981	RPMI-8226 Immunitoxicity:	0.737
A549 Cytotoxicity:	0.975	Hek293 Cytotoxicity:	0.865
BCF:	0.78 ? 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:	3.49 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.986 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.048 ? 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
NPO14922	Tarenna attenuata	Species	Rubiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[16792422]
NPO14922	Tarenna attenuata	Species	Rubiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[17343407]
NPO14922	Tarenna attenuata	Species	Rubiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO14922	Tarenna attenuata	Species	Rubiaceae	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	4
IC50	1

Activity Type	# Activity
Cell line	4
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
NPT681	Cell line	PC-12	Rattus norvegicus	Activity	=	51.9	%	PMID[8350087]
NPT681	Cell line	PC-12	Rattus norvegicus	Activity	=	54.3	%	PMID[10425121]
NPT681	Cell line	PC-12	Rattus norvegicus	Activity	=	54.7	%	PubChem BioAssay data set
NPT681	Cell line	PC-12	Rattus norvegicus	Activity	=	54.1	%	PMID[18183025]
NPT1	Others	Radical scavenging activity	n.a.	IC50	=	87000.0	nM	PMID[18183025]

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 NPC470826 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	22921
0.1-0.2	23712
0.2-0.3	2744
0.3-0.4	324
0.4-0.5	109
0.5-0.6	30
0.6-0.7	6
0.7-0.8	0
0.8-0.85	2
0.85-0.9	1
0.9-0.95	2
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.931	High Similarity	NPC470098
0.931	High Similarity	NPC473266
0.8852	High Similarity	NPC470097
0.803	Intermediate Similarity	NPC114119
0.803	Intermediate Similarity	NPC471415
0.7941	Intermediate Similarity	NPC324517
0.7941	Intermediate Similarity	NPC321972
0.7536	Intermediate Similarity	NPC473236
0.7101	Intermediate Similarity	NPC320671
0.6901	Remote Similarity	NPC324492
0.6901	Remote Similarity	NPC317053
0.6812	Remote Similarity	NPC328567
0.6066	Remote Similarity	NPC126409
0.6066	Remote Similarity	NPC99572
0.6032	Remote Similarity	NPC310854
0.597	Remote Similarity	NPC7903
0.597	Remote Similarity	NPC160991
0.5833	Remote Similarity	NPC165155
0.5833	Remote Similarity	NPC24490
0.5821	Remote Similarity	NPC16208
0.5658	Remote Similarity	NPC51328
0.5658	Remote Similarity	NPC55158
0.5571	Remote Similarity	NPC267291
0.5571	Remote Similarity	NPC481839
0.5541	Remote Similarity	NPC216129
0.5541	Remote Similarity	NPC130449
0.5541	Remote Similarity	NPC248132
0.5429	Remote Similarity	NPC75695
0.541	Remote Similarity	NPC115207
0.541	Remote Similarity	NPC158079
0.541	Remote Similarity	NPC228346
0.541	Remote Similarity	NPC40432
0.541	Remote Similarity	NPC161557
0.5316	Remote Similarity	NPC43065
0.5303	Remote Similarity	NPC185071
0.5303	Remote Similarity	NPC27843
0.5303	Remote Similarity	NPC7171
0.5254	Remote Similarity	NPC141765
0.5254	Remote Similarity	NPC34103
0.5244	Remote Similarity	NPC260397
0.5224	Remote Similarity	NPC35932
0.5224	Remote Similarity	NPC184447
0.5072	Remote Similarity	NPC9370
0.5072	Remote Similarity	NPC287495
0.5063	Remote Similarity	NPC286235

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC470826 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	4515
0.1-0.2	4515
0.2-0.3	117
0.3-0.4	3
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