NPASS Compound

Natural Product: NPC328928

Natural Product ID	NPC328928
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Hyponine E
IUPAC Name	n.a.
Synonyms	Hyponine E
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL501685
PubChem CID	44583772
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000279] Alkaloids 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 114120 0 0 0 0 0 0 0 0999 V2000 4.7225 1.7307 -2.3156 C 0 0 0 0 0 0 0 0 0 0 0 0 4.8012 0.6644 -1.2472 C 0 0 0 0 0 0 0 0 0 0 0 0 5.0955 1.2253 0.1106 C 0 0 0 0 0 0 0 0 0 0 0 0 3.9232 1.9713 0.6654 C 0 0 0 0 0 0 0 0 0 0 0 0 4.0563 3.1586 1.0056 O 0 0 0 0 0 0 0 0 0 0 0 0 2.7127 1.3747 0.8103 O 0 0 0 0 0 0 0 0 0 0 0 0 1.5054 1.8575 1.3178 C 0 0 0 0 0 0 0 0 0 0 0 0 0.7346 2.5725 0.3067 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.3741 1.8997 -0.4245 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.0838 0.8029 0.3512 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.8859 -0.0884 -0.5935 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.4306 -1.4477 -0.8538 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.3456 -2.0097 0.0265 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.4551 -1.3505 1.4006 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0404 0.0245 1.0305 C 0 0 0 0 0 0 0 0 0 0 0 0 0.7925 0.7286 2.0449 C 0 0 0 0 0 0 0 0 0 0 0 0 0.2732 1.0192 3.3782 C 0 0 0 0 0 0 0 0 0 0 0 0 1.8512 -0.2128 2.2880 O 0 0 0 0 0 0 0 0 0 0 0 0 0.9626 -0.1859 0.0271 O 0 0 0 0 0 0 0 0 0 0 0 0 0.9280 -1.4287 -0.4448 C 0 0 0 0 0 0 0 0 0 0 0 0 2.1034 -2.3283 -0.0758 C 0 0 0 0 0 0 0 0 0 0 0 0 3.2739 -1.8476 -0.6824 O 0 0 0 0 0 0 0 0 0 0 0 0 4.5384 -2.2959 -0.6558 C 0 0 0 0 0 0 0 0 0 0 0 0 4.7621 -3.3512 0.0313 O 0 0 0 0 0 0 0 0 0 0 0 0 5.6735 -1.6893 -1.3357 C 0 0 0 0 0 0 0 0 0 0 0 0 5.8018 -0.3396 -1.6068 C 0 0 0 0 0 0 0 0 0 0 0 0 6.9060 0.0828 -2.2399 N 0 0 0 0 0 0 0 0 0 0 0 0 7.9087 -0.7088 -2.6365 C 0 0 0 0 0 0 0 0 0 0 0 0 7.8074 -2.0680 -2.3779 C 0 0 0 0 0 0 0 0 0 0 0 0 6.6915 -2.5265 -1.7332 C 0 0 0 0 0 0 0 0 0 0 0 0 1.0328 -1.3573 -1.9747 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7521 -1.4974 1.8571 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.0119 -2.1152 3.0892 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.0106 -2.5148 3.7314 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.3545 -2.2868 3.6001 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.5349 -1.9054 3.0122 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.5659 -2.2789 3.8761 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.9388 -2.8741 4.9533 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.6610 -2.8486 4.7352 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.5415 -2.3456 -0.8919 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.9179 -3.0634 -2.0148 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.2096 -2.8815 -3.0379 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.0502 -3.9767 -2.0486 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.8737 -4.2310 -0.9796 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.9124 -5.1072 -1.1111 N 0 0 0 0 0 0 0 0 0 0 0 0 -6.1882 -5.7535 -2.2484 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.3812 -5.5239 -3.3486 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.3187 -4.6333 -3.2293 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.2660 -0.1725 -0.1763 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.3109 0.3600 -0.8727 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.0931 0.9667 -1.9474 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.6890 0.2079 -0.3393 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.1460 1.4832 1.1498 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7906 2.4542 2.0466 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.6619 3.1572 2.8416 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.8880 2.9150 2.7650 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.1692 4.1815 3.7721 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.3685 2.8991 -0.6974 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.7763 3.2411 -1.9684 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.2744 2.6756 -2.9835 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.8092 4.2721 -2.2426 C 0 0 0 0 0 0 0 0 0 0 0 0 1.6055 3.2076 -0.6244 O 0 0 0 0 0 0 0 0 0 0 0 0 1.7673 4.5486 -0.7931 C 0 0 0 0 0 0 0 0 0 0 0 0 1.0864 5.2880 -0.0608 O 0 0 0 0 0 0 0 0 0 0 0 0 2.7205 5.1133 -1.8128 C 0 0 0 0 0 0 0 0 0 0 0 0 5.5417 0.1938 1.1112 C 0 0 0 0 0 0 0 0 0 0 0 0 3.7086 2.0925 -2.5010 H 0 0 0 0 0 0 0 0 0 0 0 0 5.0639 1.2388 -3.2696 H 0 0 0 0 0 0 0 0 0 0 0 0 5.4540 2.5458 -2.1391 H 0 0 0 0 0 0 0 0 0 0 0 0 3.7516 0.2228 -1.2635 H 0 0 0 0 0 0 0 0 0 0 0 0 5.9326 1.9688 -0.0385 H 0 0 0 0 0 0 0 0 0 0 0 0 1.8038 2.5649 2.1554 H 0 0 0 0 0 0 0 0 0 0 0 0 0.2741 3.4757 0.8223 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.1069 1.5042 -1.3989 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.9558 0.4862 -1.5573 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.0220 -1.5078 -1.8992 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.3786 -3.0829 0.1683 H 0 0 0 0 0 0 0 0 0 0 0 0 0.2547 -1.7809 2.1298 H 0 0 0 0 0 0 0 0 0 0 0 0 0.3808 2.1263 3.5869 H 0 0 0 0 0 0 0 0 0 0 0 0 0.9246 0.6169 4.2336 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.7069 0.6087 3.6555 H 0 0 0 0 0 0 0 0 0 0 0 0 2.3530 0.1244 3.0598 H 0 0 0 0 0 0 0 0 0 0 0 0 2.1766 -2.5743 0.9766 H 0 0 0 0 0 0 0 0 0 0 0 0 1.8764 -3.3068 -0.6004 H 0 0 0 0 0 0 0 0 0 0 0 0 8.7931 -0.3327 -3.1495 H 0 0 0 0 0 0 0 0 0 0 0 0 8.6264 -2.7010 -2.7037 H 0 0 0 0 0 0 0 0 0 0 0 0 6.6421 -3.6088 -1.5436 H 0 0 0 0 0 0 0 0 0 0 0 0 0.7465 -2.3069 -2.4564 H 0 0 0 0 0 0 0 0 0 0 0 0 2.1360 -1.2592 -2.2197 H 0 0 0 0 0 0 0 0 0 0 0 0 0.5952 -0.4493 -2.4049 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.6799 -1.4090 2.0637 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.6304 -2.1603 3.7852 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.4736 -3.2812 5.8164 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.6727 -3.7242 -0.0551 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.0131 -6.4495 -2.3542 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.5910 -6.0403 -4.2792 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.7199 -4.4947 -4.1302 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.9111 -0.8898 -0.3733 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.6874 0.4940 0.7397 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.4285 0.8051 -0.8834 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.7915 2.0124 0.3784 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.8673 0.7736 1.6224 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.0866 4.3435 3.6486 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.3620 3.9139 4.8466 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.6569 5.1736 3.6222 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.3660 4.5305 -1.3239 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.4805 3.8828 -3.0132 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.2992 5.1719 -2.6528 H 0 0 0 0 0 0 0 0 0 0 0 0 2.5452 6.2127 -1.8542 H 0 0 0 0 0 0 0 0 0 0 0 0 3.7311 4.9828 -1.3673 H 0 0 0 0 0 0 0 0 0 0 0 0 2.6079 4.6149 -2.7834 H 0 0 0 0 0 0 0 0 0 0 0 0 4.6868 -0.4055 1.4902 H 0 0 0 0 0 0 0 0 0 0 0 0 6.3043 -0.4895 0.7166 H 0 0 0 0 0 0 0 0 0 0 0 0 6.0204 0.7350 1.9892 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 2 0 4 6 1 0 6 7 1 0 7 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 16 18 1 0 15 19 1 0 19 20 1 0 20 21 1 0 21 22 1 0 22 23 1 0 23 24 2 0 23 25 1 0 25 26 2 0 26 27 1 0 27 28 2 0 28 29 1 0 29 30 2 0 20 31 1 0 14 32 1 0 32 33 1 0 33 34 2 0 33 35 1 0 35 36 2 0 36 37 1 0 37 38 2 0 38 39 1 0 12 40 1 0 40 41 1 0 41 42 2 0 41 43 1 0 43 44 2 0 44 45 1 0 45 46 2 0 46 47 1 0 47 48 2 0 11 49 1 0 49 50 1 0 50 51 2 0 50 52 1 0 10 53 1 0 53 54 1 0 54 55 1 0 55 56 2 0 55 57 1 0 9 58 1 0 58 59 1 0 59 60 2 0 59 61 1 0 8 62 1 0 62 63 1 0 63 64 2 0 63 65 1 0 3 66 1 0 26 2 1 0 16 7 1 0 15 10 1 0 20 13 1 0 30 25 1 0 39 35 1 0 48 43 1 0 1 67 1 0 1 68 1 0 1 69 1 0 2 70 1 0 3 71 1 0 7 72 1 0 8 73 1 0 9 74 1 0 11 75 1 0 12 76 1 0 13 77 1 0 14 78 1 0 17 79 1 0 17 80 1 0 17 81 1 0 18 82 1 0 21 83 1 0 21 84 1 0 28 85 1 0 29 86 1 0 30 87 1 0 31 88 1 0 31 89 1 0 31 90 1 0 36 91 1 0 37 92 1 0 38 93 1 0 44 94 1 0 46 95 1 0 47 96 1 0 48 97 1 0 52 98 1 0 52 99 1 0 52100 1 0 53101 1 0 53102 1 0 57103 1 0 57104 1 0 57105 1 0 61106 1 0 61107 1 0 61108 1 0 65109 1 0 65110 1 0 65111 1 0 66112 1 0 66113 1 0 66114 1 0 M END

Standard InCHIKey	PMRSIAJYXABCTQ-IWYQQVOHSA-N
Standard InCHI	InChI=1S/C45H48N2O19/c1-21-22(2)38(52)65-35-33(60-24(4)49)37(62-26(6)51)44(20-58-23(3)48)36(61-25(5)50)32(63-39(53)27-12-9-15-46-18-27)30-34(64-41(55)29-14-11-17-57-29)45(44,43(35,8)56)66-42(30,7)19-59-40(54)28-13-10-16-47-31(21)28/h9-18,21-22,30,32-37,56H,19-20H2,1-8H3/t21?,22?,30-,32-,33+,34-,35+,36-,37+,42+,43+,44-,45+/m1/s1
SMILES	CC1C(C(=O)OC2C(C(C3(C(C(C4C(C3(C2(C)O)OC4(COC(=O)C5=C1N=CC=C5)C)OC(=O)C6=CC=CO6)OC(=O)C7=CN=CC=C7)OC(=O)C)COC(=O)C)OC(=O)C)OC(=O)C)C

Calculated Properties

Physi-Chem Properties

Molecular Weight:	920.29	Volume:	873.805 ? Van der Waals volume.
Dense:	1.053	LogP:	0.971 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	1.159 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.405 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	15.0	Rigid Bonds:	48.0
TPSA:	278.78 ? Topological Polar Surface Area.	H-Bond Acceptor:	21.0
H-Bond Donor:	1.0	Rings:	7.0
Heavy Atoms:	21.0

MedChem Properties

QED Drug-Likeness Score:	0.238	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	7.785	Fsp³:	0.511
MCE-18:	238.235 ? 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:	0.053	Fluc inhibitor:	0.001 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.004 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.12 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.01	Promiscuous compounds:	0.005

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.472	MDCK Permeability:	-4.979
Pgp-inhibitor:	0.193	Pgp-substrate:	0.555
PAMPA:	0.989 ? 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%):	0.01	30% Bioavailability (F30%):	0.417
50% Bioavailability (F50%):	0.922

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.005	MRP1:	1.0
Plasma Protein Binding (PPB):	55.188%	Volume Distribution (VD):	-0.355
Fu:	45.405% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.003
OATP1B3 inhibitor:	0.375	BCRP inhibitor:	0.0
BSEP inhibitor:	0.994

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.001
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.0	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.806
CYP3A4-inhibitor:	0.451	CYP3A4-substrate:	0.0
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	1.0
HLM stability:	0.995 ? 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):

0.264

Half-life (T1/2):

1.658

ADMET: Toxicity

hERG Blockers:	0.012	hERG Blockers (10um):	0.162
Human Hepatotoxicity (H-HT):	0.29	Drug-induced Liver Injury (DILI):	0.999
AMES Toxicity:	0.584	Rat Oral Acute Toxicity:	0.063
Maximum Recommended Daily Dose:	0.334	Skin Sensitization:	0.988
Carcinogencity:	0.886	Eye Corrosion:	0.0
Eye Irritation:	0.0	Respiratory Toxicity:	0.0
Drug-induced Neurotoxicity:	0.589	Ototoxicity:	0.932
Hematotoxicity:	0.06	Drug-induced Nephrotoxicity:	0.952
Genotoxicity:	0.961	RPMI-8226 Immunitoxicity:	0.177
A549 Cytotoxicity:	0.008	Hek293 Cytotoxicity:	0.277
BCF:	0.746 ? 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:	3.527 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.655 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	5.04 ? 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
NPO1152	Tripterygium hypoglaucum	Species	Celastraceae	Eukaryota	n.a.	root	n.a.	DOI[10.1016/S0040-4039(99)00339-1]
NPO1152	Tripterygium hypoglaucum	Species	Celastraceae	Eukaryota	n.a.	root	n.a.	PMID[10746886]
NPO1152	Tripterygium hypoglaucum	Species	Celastraceae	Eukaryota	n.a.	n.a.	n.a.	PMID[10757718]
NPO1152	Tripterygium hypoglaucum	Species	Celastraceae	Eukaryota	root bark	Kunming, Yunnan, China	n.a.	PMID[10757718]
NPO1152	Tripterygium hypoglaucum	Species	Celastraceae	Eukaryota	n.a.	root	n.a.	PMID[10757718]
NPO1152	Tripterygium hypoglaucum	Species	Celastraceae	Eukaryota	n.a.	root	n.a.	PMID[22256754]
NPO1152	Tripterygium hypoglaucum	Species	Celastraceae	Eukaryota	n.a.	n.a.	n.a.	PMID[22256754]
NPO1152	Tripterygium hypoglaucum	Species	Celastraceae	Eukaryota	n.a.	root	n.a.	PMID[23252270]
NPO1152	Tripterygium hypoglaucum	Species	Celastraceae	Eukaryota	n.a.	n.a.	n.a.	PMID[2534610]
NPO1152	Tripterygium hypoglaucum	Species	Celastraceae	Eukaryota	n.a.	n.a.	n.a.	Europe PMC[535601]
NPO1152	Tripterygium hypoglaucum	Species	Celastraceae	Eukaryota	n.a.	n.a.	n.a.	PMID[8328267]
NPO1152	Tripterygium hypoglaucum	Species	Celastraceae	Eukaryota	n.a.	root	n.a.	Database[Article]
NPO1152	Tripterygium hypoglaucum	Species	Celastraceae	Eukaryota	n.a.	leaf	n.a.	Database[Article]
NPO1152	Tripterygium hypoglaucum	Species	Celastraceae	Eukaryota	n.a.	n.a.	n.a.	Database[Article]
NPO1152	Tripterygium hypoglaucum	Species	Celastraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO1152	Tripterygium hypoglaucum	Species	Celastraceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO1152	Tripterygium hypoglaucum	Species	Celastraceae	Eukaryota	n.a.	n.a.	n.a.	PMID[Phytochemistry, 2000, 53, 715-722.]
NPO1152	Tripterygium hypoglaucum	Species	Celastraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO1152	Tripterygium hypoglaucum	Species	Celastraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO1152	Tripterygium hypoglaucum	Species	Celastraceae	Eukaryota	root bark	Kunming, Yunnan, China	n.a.	Database[Title]
NPO1152	Tripterygium hypoglaucum	Species	Celastraceae	Eukaryota	n.a.	n.a.	n.a.	Database[Title]
NPO1152	Tripterygium hypoglaucum	Species	Celastraceae	Eukaryota	root bark	n.a.	n.a.	Database[Title]
NPO1152	Tripterygium hypoglaucum	Species	Celastraceae	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
IC50	1
EC50	1

Activity Type	# Activity
Cell line	1
Organism	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
NPT759	Cell line	H9	Homo sapiens	IC50	=	1.95	ug.mL-1	PMID[10757718]
NPT24	Organism	Human immunodeficiency virus 1	Human immunodeficiency virus 1	EC50	=	0.17	ug.mL-1	PMID[10757718]

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 NPC328928 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	25877
0.1-0.2	23201
0.2-0.3	608
0.3-0.4	91
0.4-0.5	20
0.5-0.6	27
0.6-0.7	22
0.7-0.8	0
0.8-0.85	1
0.85-0.9	1
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.8866	High Similarity	NPC475301
0.82	Intermediate Similarity	NPC326930
0.785	Intermediate Similarity	NPC327769
0.7778	Intermediate Similarity	NPC76565
0.7778	Intermediate Similarity	NPC601313
0.7692	Intermediate Similarity	NPC87152
0.7524	Intermediate Similarity	NPC475631
0.729	Intermediate Similarity	NPC475596
0.713	Intermediate Similarity	NPC476110
0.7054	Intermediate Similarity	NPC483853
0.7054	Intermediate Similarity	NPC608314
0.7037	Intermediate Similarity	NPC475600
0.6944	Remote Similarity	NPC475303
0.6887	Remote Similarity	NPC473833
0.6827	Remote Similarity	NPC35208
0.6639	Remote Similarity	NPC483856
0.6606	Remote Similarity	NPC53255
0.6606	Remote Similarity	NPC85879
0.65	Remote Similarity	NPC483854
0.6496	Remote Similarity	NPC475426
0.6449	Remote Similarity	NPC475137
0.6446	Remote Similarity	NPC482915
0.633	Remote Similarity	NPC475498
0.6316	Remote Similarity	NPC30456
0.6316	Remote Similarity	NPC488904
0.6283	Remote Similarity	NPC470486
0.6228	Remote Similarity	NPC13603
0.6204	Remote Similarity	NPC250807
0.6204	Remote Similarity	NPC57797
0.6195	Remote Similarity	NPC475533
0.6174	Remote Similarity	NPC475644
0.6154	Remote Similarity	NPC319880
0.6154	Remote Similarity	NPC320324
0.6053	Remote Similarity	NPC328186
0.5983	Remote Similarity	NPC600607
0.5966	Remote Similarity	NPC327904
0.5948	Remote Similarity	NPC324619
0.5932	Remote Similarity	NPC600583
0.5917	Remote Similarity	NPC471979
0.5882	Remote Similarity	NPC477787
0.5862	Remote Similarity	NPC316841
0.5862	Remote Similarity	NPC471977
0.5841	Remote Similarity	NPC146824
0.5833	Remote Similarity	NPC38959
0.5818	Remote Similarity	NPC470306
0.5667	Remote Similarity	NPC244839
0.5641	Remote Similarity	NPC122968
0.5641	Remote Similarity	NPC228377
0.5593	Remote Similarity	NPC475315
0.5504	Remote Similarity	NPC483855
0.5447	Remote Similarity	NPC170751
0.5417	Remote Similarity	NPC471190
0.5328	Remote Similarity	NPC473689
0.5328	Remote Similarity	NPC292416
0.5304	Remote Similarity	NPC471016
0.5289	Remote Similarity	NPC600224
0.5203	Remote Similarity	NPC611166
0.5164	Remote Similarity	NPC604935
0.5161	Remote Similarity	NPC475406
0.5161	Remote Similarity	NPC601643
0.5086	Remote Similarity	NPC473850

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC328928 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	5394
0.1-0.2	3726
0.2-0.3	30
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